Deep Learning for Detection and Segmentation in High-Content Microscopy Images

High-content microscopy led to many advances in biology and medicine. This fast emerging technology is transforming cell biology into a big data driven science. Computer vision methods are used to automate the analysis of microscopy image data. In recent years, deep learning became popular and had major success in computer vision. Most of the available methods are developed to process natural images. Compared to natural images, microscopy images pose domain specific challenges such as small training datasets, clustered objects, and class imbalance. In this thesis, new deep learning methods for object detection and cell segmentation in microscopy images are introduced. For particle detection in fluorescence microscopy images, a deep learning method based on a domain-adapted Deconvolution Network is presented. In addition, a method for mitotic cell detection in heterogeneous histopathology images is proposed, which combines a deep residual network with Hough voting. The method is used for grading of whole-slide histology images of breast carcinoma. Moreover, a method for both particle detection and cell detection based on object centroids is introduced, which is trainable end-to-end. It comprises a novel Centroid Proposal Network, a layer for ensembling detection hypotheses over image scales and anchors, an anchor regularization scheme which favours prior anchors over regressed locations, and an improved algorithm for Non-Maximum Suppression. Furthermore, a novel loss function based on Normalized Mutual Information is proposed which can cope with strong class imbalance and is derived within a Bayesian framework. For cell segmentation, a deep neural network with increased receptive field to capture rich semantic information is introduced. Moreover, a deep neural network which combines both paradigms of multi-scale feature aggregation of Convolutional Neural Networks and iterative refinement of Recurrent Neural Networks is proposed. To increase the robustness of the training and improve segmentation, a novel focal loss function is presented. In addition, a framework for black-box hyperparameter optimization for biomedical image analysis pipelines is proposed. The framework has a modular architecture that separates hyperparameter sampling and hyperparameter optimization. A visualization of the loss function based on infimum projections is suggested to obtain further insights into the optimization problem. Also, a transfer learning approach is presented, which uses only one color channel for pre-training and performs fine-tuning on more color channels. Furthermore, an approach for unsupervised domain adaptation for histopathological slides is presented. Finally, Galaxy Image Analysis is presented, a platform for web-based microscopy image analysis. Galaxy Image Analysis workflows for cell segmentation in cell cultures, particle detection in mice brain tissue, and MALDI/H&E image registration have been developed. The proposed methods were applied to challenging synthetic as well as real microscopy image data from various microscopy modalities. It turned out that the proposed methods yield state-of-the-art or improved results. The methods were benchmarked in international image analysis challenges and used in various cooperation projects with biomedical researchers

Blood Cell Classification Using the Hough Transform and Convolutional Neural Networks

https://doi.org/10.1007/978-3-319-77712-2_62The detection of red blood cells in blood samples can be crucial for the disease detection in its early stages. The use of image processing techniques can accelerate and improve the effectiveness and efficiency of this detection. In this work, the use of the Circle Hough transform for cell detection and artificial neural networks for their identification as a red blood cell is proposed. Specifically, the application of neural networks (MLP) as a standard classification technique with (MLP) is compared with new proposals related to deep learning such as convolutional neural networks (CNNs). The different experiments carried out reveal the high classification ratio and show promising results after the application of the CNNs.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Augmented Mitotic Cell Count using Field Of Interest Proposal

Histopathological prognostication of neoplasia including most tumor grading systems are based upon a number of criteria. Probably the most important is the number of mitotic figures which are most commonly determined as the mitotic count (MC), i.e. number of mitotic figures within 10 consecutive high power fields. Often the area with the highest mitotic activity is to be selected for the MC. However, since mitotic activity is not known in advance, an arbitrary choice of this region is considered one important cause for high variability in the prognostication and grading. In this work, we present an algorithmic approach that first calculates a mitotic cell map based upon a deep convolutional network. This map is in a second step used to construct a mitotic activity estimate. Lastly, we select the image segment representing the size of ten high power fields with the overall highest mitotic activity as a region proposal for an expert MC determination. We evaluate the approach using a dataset of 32 completely annotated whole slide images, where 22 were used for training of the network and 10 for test. We find a correlation of r=0.936 in mitotic count estimate.Comment: 6 pages, submitted to BVM 2019 (bvm-workshop.org

Class-Agnostic Counting

Nearly all existing counting methods are designed for a specific object class. Our work, however, aims to create a counting model able to count any class of object. To achieve this goal, we formulate counting as a matching problem, enabling us to exploit the image self-similarity property that naturally exists in object counting problems. We make the following three contributions: first, a Generic Matching Network (GMN) architecture that can potentially count any object in a class-agnostic manner; second, by reformulating the counting problem as one of matching objects, we can take advantage of the abundance of video data labeled for tracking, which contains natural repetitions suitable for training a counting model. Such data enables us to train the GMN. Third, to customize the GMN to different user requirements, an adapter module is used to specialize the model with minimal effort, i.e. using a few labeled examples, and adapting only a small fraction of the trained parameters. This is a form of few-shot learning, which is practical for domains where labels are limited due to requiring expert knowledge (e.g. microbiology). We demonstrate the flexibility of our method on a diverse set of existing counting benchmarks: specifically cells, cars, and human crowds. The model achieves competitive performance on cell and crowd counting datasets, and surpasses the state-of-the-art on the car dataset using only three training images. When training on the entire dataset, the proposed method outperforms all previous methods by a large margin.Comment: Asian Conference on Computer Vision (ACCV), 201

Stacked Denoising Autoencoders and Transfer Learning for Immunogold Particles Detection and Recognition

In this paper we present a system for the detection of immunogold particles and a Transfer Learning (TL) framework for the recognition of these immunogold particles. Immunogold particles are part of a high-magnification method for the selective localization of biological molecules at the subcellular level only visible through Electron Microscopy. The number of immunogold particles in the cell walls allows the assessment of the differences in their compositions providing a tool to analise the quality of different plants. For its quantization one requires a laborious manual labeling (or annotation) of images containing hundreds of particles. The system that is proposed in this paper can leverage significantly the burden of this manual task. For particle detection we use a LoG filter coupled with a SDA. In order to improve the recognition, we also study the applicability of TL settings for immunogold recognition. TL reuses the learning model of a source problem on other datasets (target problems) containing particles of different sizes. The proposed system was developed to solve a particular problem on maize cells, namely to determine the composition of cell wall ingrowths in endosperm transfer cells. This novel dataset as well as the code for reproducing our experiments is made publicly available. We determined that the LoG detector alone attained more than 84\% of accuracy with the F-measure. Developing immunogold recognition with TL also provided superior performance when compared with the baseline models augmenting the accuracy rates by 10\%