ConCORDe-Net: Cell Count Regularized Convolutional Neural Network for Cell Detection in Multiplex Immunohistochemistry Images

In digital pathology, cell detection and classification are often prerequisites to quantify cell abundance and explore tissue spatial heterogeneity. However, these tasks are particularly challenging for multiplex immunohistochemistry (mIHC) images due to high levels of variability in staining, expression intensity, and inherent noise as a result of preprocessing artefacts. We proposed a deep learning method to detect and classify cells in mIHC whole-tumour slide images of breast cancer. Inspired by inception-v3, we developed Cell COunt RegularizeD Convolutional neural Network (ConCORDe-Net) which integrates conventional dice overlap and a new cell count loss function for optimizing cell detection, followed by a multi-stage convolutional neural network for cell classification. In total, 20447 cells, belonging to five cell classes were annotated by experts from 175 patches extracted from 6 whole-tumour mIHC images. These patches were randomly split into training, validation and testing sets. Using ConCORDe-Net, we obtained a cell detection F1 score of 0.873, which is the best score compared to three state of the art methods. In particular, ConCORDe-Net excels at detecting closely located and weakly stained cells compared to other methods. Incorporating cell count loss in the objective function regularizes the network to learn weak gradient boundaries and separate weakly stained cells from background artefacts. Moreover, cell classification accuracy of 96.5% was achieved. These results support that incorporating problem-specific knowledge such as cell count into deep learning-based cell detection architectures improve the robustness of the algorithm.

DeepSDCS: Dissecting cancer proliferation heterogeneity in Ki67 digital whole slide images

Ki67 is an important biomarker for breast cancer. Classification of positive and negative Ki67 cells in histology slides is a common approach to determine cancer proliferation status. However, there is a lack of generalizable and accurate methods to automate Ki67 scoring in large-scale patient cohorts. In this work, we have employed a novel deep learning technique based on hypercolumn descriptors for cell classification in Ki67 images. Specifically, we developed the Simultaneous Detection and Cell Segmentation (DeepSDCS) network to perform cell segmentation and detection. VGG16 network was used for the training and fine tuning to training data. We extracted the hypercolumn descriptors of each cell to form the vector of activation from specific layers to capture features at different granularity. Features from these layers that correspond to the same pixel were propagated using a stochastic gradient descent optimizer to yield the detection of the nuclei and the final cell segmentations. Subsequently, seeds generated from cell segmentation were propagated to a spatially constrained convolutional neural network for the classification of the cells into stromal, lymphocyte, Ki67-positive cancer cell, and Ki67-negative cancer cell. We validated its accuracy in the context of a large-scale clinical trial of oestrogen-receptor-positive breast cancer. We achieved 99.06% and 89.59% accuracy on two separate test sets of Ki67 stained breast cancer dataset comprising biopsy and whole-slide images.