Abstract

Tissue microarray (TMA) core images are a treasure trove for artificial intelligence applications. However, a common problem of TMAs is multiple sectioning, which can change the content of the intended tissue core and requires re-labelling. Here, we investigate different ensemble methods for colorectal tissue classification using high-throughput TMAs. Hematoxylin and Eosin (H&E) core images of 0.6 mm or 1.0 mm diameter from three international cohorts were extracted from 54 digital slides (n = 15,150 cores). After TMA core extraction and color enhancement, five different flows of independent and ensemble deep learning were applied. Training and testing data with 2144 and 13,006 cores included three classes: tumor, normal or “other” tissue. Ground-truth data were collected from 30 ngTMA slides (n = 8689 cores). A test augmentation is applied to reduce the uncertain prediction. Predictive accuracy of the best method, namely Soft Voting Ensemble of one VGG and one CapsNet models was 0.982, 0.947 and 0.939 for normal, “other” and tumor, which outperformed to independent or ensemble learning with one base-estimator. Our high-accuracy algorithm for colorectal tissue classification in high-throughput TMAs is amenable to images from different institutions, core sizes and stain intensity. It helps to reduce error in TMA core evaluations with previously given labels.

Highlights

  • Tissue microarray (TMA) core images are a treasure trove for artificial intelligence applications

  • In order to produce a single image from the larger next-generation Tissue Microarray (ngTMA) scan, we find the contour of the TMA core at lowest level of image resolution by applying a gray intensity threshold on the Gaussian blurring and smoothing image

  • Considering the evaluation B: comparison of the algorithms to the ground truth, we applied all five deep learning flows on a further 8689 TMA cores from 30 slides, where 21 slides, 4 slides and 5 slides were punched in the area of tumor center, of normal colonic tissue and of tumor stroma, respectively

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Summary

Introduction

Tissue microarray (TMA) core images are a treasure trove for artificial intelligence applications. We investigate different ensemble methods for colorectal tissue classification using high-throughput TMAs. Hematoxylin and Eosin (H&E) core images of 0.6 mm or 1.0 mm diameter from three international cohorts were extracted from 54 digital slides (n = 15,150 cores). Our high-accuracy algorithm for colorectal tissue classification in high-throughput TMAs is amenable to images from different institutions, core sizes and stain intensity. It helps to reduce error in TMA core evaluations with previously given labels. A massive archive of tumor/normal tissue ngTMAs has been generated along with their corresponding single-core images after H&E or immunohistochemistry staining Despite these advantages, TMAs are not without some ­drawbacks[9]: serial sectioning of the TMA block will inevitably lead to shifts in the expected tissue content within each core. The shift in tissue content through this “z-axis” requires re-labelling of each tissue core in order to avoid any error carried through into steps, a task which can be tedious, especially with high-throughput TMA sets containing thousands of tissue cores

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