Abstract

The mitotic activity index is a key prognostic measure in tumour grading. Microscopy based detection of mitotic nuclei is a significant overhead and necessitates automation. This work proposes deep CNN based multi-phase mitosis detection framework “MP-MitDet” for mitotic nuclei identification in breast cancer histopathological images. The workflow constitutes: (1) label-refiner, (2) tissue-level mitotic region selection, (3) blob analysis, and (4) cell-level refinement. We developed an automatic label-refiner to represent weak labels with semi-sematic information for training of deep CNNs. A deep instance-based detection and segmentation model is used to explore probable mitotic regions on tissue patches. More probable regions are screened based on blob area and then analysed at cell-level by developing a custom CNN classifier “MitosRes-CNN” to filter false mitoses. The performance of the proposed “MitosRes-CNN” is compared with the state-of-the-art CNNs that are adapted to cell-level discrimination through cross-domain transfer learning and by adding task-specific layers. The performance of the proposed framework shows good discrimination ability in terms of F-score (0.75), recall (0.76), precision (0.71) and area under the precision-recall curve (0.78) on challenging TUPAC16 dataset. Promising results suggest good generalization of the proposed framework that can learn characteristic features from heterogenous mitotic nuclei.

Highlights

  • The mitotic activity index is a key prognostic measure in tumour grading

  • This study aims to develop a mitosis detection framework that can effectively learn the mitosis representation from the weakly labelled histopathological images

  • Mitosis detection module (Fig. 7) is further divided into: (1) mitotic region selection at tissue-level via deep instance-based detection and segmentation model, (2) blob analysis, and (3) mitotic region enhancement at cell-level via deep convolutional neural networks (CNNs) classifier to establish the balance between detection rate and precision

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Summary

Introduction

The mitotic activity index is a key prognostic measure in tumour grading. Microscopy based detection of mitotic nuclei is a significant overhead and necessitates automation. This work proposes deep CNN based multi-phase mitosis detection framework “MP-MitDet” for mitotic nuclei identification in breast cancer histopathological images. We developed an automatic label-refiner to represent weak labels with semi-sematic information for training of deep CNNs. A deep instance-based detection and segmentation model is used to explore probable mitotic regions on tissue patches. To address all of the above mentioned challenges, in this study we have proposed a new learning framework for weakly labelled dataset A deep instance-based detection and segmentation CNN is employed on tissue level to localize the probable mitotic regions, neglecting numerous non-mitotic nuclei. The contributions of the proposed framework are the following: Scientific Reports | (2021) 11:6215 |

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