Understanding the morphological changes of primary neuronal cells induced by chemical compounds is essential for drug discovery. Using the data from a single high-throughput imaging assay, a classification model for predicting the biological activity of candidate compounds was introduced. The image recognition model which is based on deep convolutional neural network (CNN) architecture with residual connections achieved accuracy of 99.6 @math on a binary classification task of distinguishing untreated and treated rodent primary neuronal cells with Amyloid- @math .
Abstract Abundant accumulation of digital histopathological images has led to the increased demand for their analysis, such as computer-aided diagnosis using machine learning techniques. However, digital pathological images and related tasks have some issues to be considered. In this mini-review, we introduce the application of digital pathological image analysis using machine learning algorithms, address some problems specific to such analysis, and propose possible solutions. The use of machine learning (ML) has been increasing rapidly in the medical imaging field, including computer-aided diagnosis (CAD), radiomics, and medical image analysis. Recently, an ML area called deep learning emerged in the computer vision field and became very popular in many fields. It started from an event in late 2012, when a deep-learning approach based on a convolutional neural network (CNN) won an overwhelming victory in the best-known worldwide computer vision competition, ImageNet Classification. Since then, researchers in virtually all fields, including medical imaging, have started actively participating in the explosively growing field of deep learning. In this paper, the area of deep learning in medical imaging is overviewed, including (1) what was changed in machine learning before and after the introduction of deep learning, (2) what is the source of the power of deep learning, (3) two major deep-learning models: a massive-training artificial neural network (MTANN) and a convolutional neural network (CNN), (4) similarities and differences between the two models, and (5) their applications to medical imaging. This review shows that ML with feature input (or feature-based ML) was dominant before the introduction of deep learning, and that the major and essential difference between ML before and after deep learning is the learning of image data directly without object segmentation or feature extraction; thus, it is the source of the power of deep learning, although the depth of the model is an important attribute. The class of ML with image input (or image-based ML) including deep learning has a long history, but recently gained popularity due to the use of the new terminology, deep learning. There are two major models in this class of ML in medical imaging, MTANN and CNN, which have similarities as well as several differences. In our experience, MTANNs were substantially more efficient in their development, had a higher performance, and required a lesser number of training cases than did CNNs. “Deep learning”, or ML with image input, in medical imaging is an explosively growing, promising field. It is expected that ML with image input will be the mainstream area in the field of medical imaging in the next few decades.  Biologists can now prepare and image thousands of samples per day using automation, enabling chemical screens and functional genomics (for example, using RNA interference). Here we describe the first free, open-source system designed for flexible, high-throughput cell image analysis, CellProfiler. CellProfiler can address a variety of biological questions quantitatively, including standard assays (for example, cell count, size, per-cell protein levels) and complex morphological assays (for example, cell organelle shape or subcellular patterns of DNA or protein staining). Summary In both academia and the pharmaceutical industry, large-scale assays for drug discovery are expensive and often impractical, particularly for the increasingly important physiologically relevant model systems that require primary cells, organoids, whole organisms, or expensive or rare reagents. We hypothesized that data from a single high-throughput imaging assay can be repurposed to predict the biological activity of compounds in other assays, even those targeting alternate pathways or biological processes. Indeed, quantitative information extracted from a three-channel microscopy-based screen for glucocorticoid receptor translocation was able to predict assay-specific biological activity in two ongoing drug discovery projects. In these projects, repurposing increased hit rates by 50- to 250-fold over that of the initial project assays while increasing the chemical structure diversity of the hits. Our results suggest that data from high-content screens are a rich source of information that can be used to predict and replace customized biological assays.  We present deep-learning-enabled super-resolution across different fluorescence microscopy modalities. This data-driven approach does not require numerical modeling of the imaging process or the estimation of a point-spread-function, and is based on training a generative adversarial network (GAN) to transform diffraction-limited input images into super-resolved ones. Using this framework, we improve the resolution of wide-field images acquired with low-numerical-aperture objectives, matching the resolution that is acquired using high-numerical-aperture objectives. We also demonstrate cross-modality super-resolution, transforming confocal microscopy images to match the resolution acquired with a stimulated emission depletion (STED) microscope. We further demonstrate that total internal reflection fluorescence (TIRF) microscopy images of subcellular structures within cells and tissues can be transformed to match the results obtained with a TIRF-based structured illumination microscope. The deep network rapidly outputs these super-resolved images, without any iterations or parameter search, and could serve to democratize super-resolution imaging. We show that deep convolutional neural networks combined with nonlinear dimension reduction enable reconstructing biological processes based on raw image data. We demonstrate this by reconstructing the cell cycle of Jurkat cells and disease progression in diabetic retinopathy. In further analysis of Jurkat cells, we detect and separate a subpopulation of dead cells in an unsupervised manner and, in classifying discrete cell cycle stages, we reach a sixfold reduction in error rate compared to a recent approach based on boosting on image features. In contrast to previous methods, deep learning based predictions are fast enough for on-the-fly analysis in an imaging flow cytometer. The histological analysis of tissue samples, widely used for disease diagnosis, involves lengthy and laborious tissue preparation. Here, we show that a convolutional neural network trained using a generative adversarial-network model can transform wide-field autofluorescence images of unlabelled tissue sections into images that are equivalent to the bright-field images of histologically stained versions of the same samples. A blind comparison, by board-certified pathologists, of this virtual staining method and standard histological staining using microscopic images of human tissue sections of the salivary gland, thyroid, kidney, liver and lung, and involving different types of stain, showed no major discordances. The virtual-staining method bypasses the typically labour-intensive and costly histological staining procedures, and could be used as a blueprint for the virtual staining of tissue images acquired with other label-free imaging modalities. Deep learning can be used to virtually stain autofluorescence images of unlabelled tissue sections, generating images that are equivalent to the histologically stained versions.   