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Whole Slide Image Registration for the Study of Tumor Heterogeneity

Part of the Lecture Notes in Computer Science book series (LNIP,volume 11039)


Consecutive thin sections of tissue samples make it possible to study local variation in e.g. protein expression and tumor heterogeneity by staining for a new protein in each section. In order to compare and correlate patterns of different proteins, the images have to be registered with high accuracy. The problem we want to solve is registration of gigapixel whole slide images (WSI). This presents 3 challenges: (i) Images are very large; (ii) Thin sections result in artifacts that make global affine registration prone to very large local errors; (iii) Local affine registration is required to preserve correct tissue morphology (local size, shape and texture). In our approach we compare WSI registration based on automatic and manual feature selection on either the full image or natural sub-regions (as opposed to square tiles). Working with natural sub-regions, in an interactive tool makes it possible to exclude regions containing scientifically irrelevant information. We also present a new way to visualize local registration quality by a Registration Confidence Map (RCM). With this method, intra-tumor heterogeneity and characteristics of the tumor microenvironment can be observed and quantified.


  • Whole slide image
  • Registration
  • Digital pathology

C. Wählby—European Research council for funding via ERC Consolidator grant 682810 to C. Wählby.

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  • DOI: 10.1007/978-3-030-00949-6_12
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Correspondence to Leslie Solorzano , Gabriela M. Almeida , Bárbara Mesquita , Diana Martins , Carla Oliveira or Carolina Wählby .

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Solorzano, L., Almeida, G.M., Mesquita, B., Martins, D., Oliveira, C., Wählby, C. (2018). Whole Slide Image Registration for the Study of Tumor Heterogeneity. In: , et al. Computational Pathology and Ophthalmic Medical Image Analysis. OMIA COMPAY 2018 2018. Lecture Notes in Computer Science(), vol 11039. Springer, Cham.

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