Deep learning and transfer learning for automatic cell counting in microscope images of human cancer cell lines

Abstract

In biology and medicine, cell counting is one of the most important elements of cytometry, with applications to research and clinical practice. For instance, the complete cell count could help to determine conditions for which cancer cells could grow or not. However, cell counting is a laborious and time-consuming process, and its automatization is highly demanded. Here, we propose use of a Convolutional Neural Network-based regressor, a regression model trained end-to-end, to provide the cell count. First, unlike most of the related work, we formulate the problem of cell counting as the regression task rather than the classification task. This allows not only to reduce the required annotation information (i.e., the number of cells instead of pixel-level annotations) but also to reduce the burden of segmenting potential cells and then classifying them. Second, we propose use of xResNet, a successful convolutional architecture with residual connection, together with transfer learning (using a pretrained model) to achieve human-level performance. We demonstrate the performance of our approach to real-life data of two cell lines, human osteosarcoma and human leukemia, collected at the University of Amsterdam (133 training images, and 32 test images). We show that the proposed method (deep learning and transfer learning) outperforms currently used machine learning methods. It achieves the test mean absolute error equal 12 (±15) against 32 (±33) obtained by the deep learning without transfer learning, and 41 (±37) of the best-performing machine learning pipeline (Random Forest Regression with the Histogram of Gradients features).