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Cell detection and counting in the image-based ELISPOT and Fluorospot immunoassays is considered a bottleneck. The task has remained hard to automatize, and biomedical researchers often have to rely on results that are not accurate. Previously proposed solutions are heuristic, and data-based solutions are subject to a lack of objective ground truth data. In this paper, we analyze a partial differential equations model for ELISPOT, Fluorospot, and assays of similar design. This leads us to a mathematical observation model for the images generated by these assays. We use this model to motivate a methodology for cell detection. Finally, we provide a real-data example that suggests that this cell detection methodology and a human expert perform comparably.
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Accurate cell detection and counting in the image-based ELISpot and FluoroSpot immunoassays is a challenging task. Recently proposed methodology matches human accuracy by leveraging knowledge of the underlying physical process of these assays and using proximal optimization methods to solve an inverse problem. Nonetheless, thousands of computationally expensive iterations are often needed to reach a near-optimal solution. In this paper, we exploit the structure of the iterations to design a parameterized computation graph, SpotNet, that learns the patterns embedded within several training images and their respective cell information. Further, we compare SpotNet to a convolutional neural network layout customized for cell detection. We show empirical evidence that, while both designs obtain a detection performance on synthetic data far beyond that of a human expert, SpotNet is easier to train and obtains better estimates of particle secretion for each cell.
Microorganisms such as bacteria and fungi play essential roles in many application fields, like biotechnique, medical technique and industrial domain. Microorganism counting techniques are crucial in microorganism analysis, helping biologists and related researchers quantitatively analyze the microorganisms and calculate their characteristics, such as biomass concentration and biological activity. However, traditional microorganism manual counting methods, such as plate counting method, hemocytometry and turbidimetry, are time-consuming, subjective and need complex operations, which are difficult to be applied in large-scale applications. In order to improve this situation, image analysis is applied for microorganism counting since the 1980s, which consists of digital image processing, image segmentation, image classification and suchlike. Image analysis-based microorganism counting methods are efficient comparing with traditional plate counting methods. In this article, we have studied the development of microorganism counting methods using digital image analysis. Firstly, the microorganisms are grouped as bacteria and other microorganisms. Then, the related articles are summarized based on image segmentation methods. Each part of the article is reviewed by methodologies. Moreover, commonly used image processing methods for microorganism counting are summarized and analyzed to find common technological points. More than 144 papers are outlined in this article. In conclusion, this paper provides new ideas for the future development trend of microorganism counting, and provides systematic suggestions for implementing integrated microorganism counting systems in the future. Researchers in other fields can refer to the techniques analyzed in this paper.
Since the beginning of this decade, CNN has been a very successful tool in the field of Computer Vision tasks.The invention of CNN was inspired from neuroscience and it shares a lot of anatomical similarities with our visual system.Inspired by the anatomyof humanvisual system, wearguethat the existing U-Net architecture can be improvedin many ways. As human visual system uses attention mechanism, we have used attention concatenation in place of normalconcatenation.Although, CNN is purely feed-forward in nature but anatomical evidences show that our brain contains recurrent synapses and they often outnumber feed-forward and top-down connections. Thisfact inspiresus to userecurrent convolution connectionsin place of normalconvolution blocksin U-Net.Thispaper also addressesthe class imbalance issuein the field of medical image analysis. The paperresolvestheproblem of class imbalanceswith the help of state-of-the-art loss functions.Weargue thatourproposed architecturecan be trained end to end with a few training data and it outperforms the other variantsof U-Net.
Convolutional neural networks, the state of the art for image segmentation, have been successfully applied to histology images by many computational researchers. However, the translatability of this technology to clinicians and biological researchers is limited due to the complex and undeveloped user interface of the code, as well as the extensive computer setup required. As an extension of our previous work (arXiv:1812.07509), we have developed a tool for segmentation of whole slide images (WSIs) with an easy to use graphical user interface. Our tool runs a state-of-the-art convolutional neural network for segmentation of WSIs in the cloud. Our plugin is built on the open source tool HistomicsTK by Kitware Inc. (Clifton Park, NY), which provides remote data management and viewing abilities for WSI datasets. The ability to access this tool over the internet will facilitate widespread use by computational non-experts. Users can easily upload slides to a server where our plugin is installed and perform human in the loop segmentation analysis remotely. This tool is open source, and has the ability to be adapted to segment of any pathological structure. For a proof of concept, we have trained it to segment glomeruli from renal tissue images, achieving an F-score > 0.97 on holdout tissue slides.
Obtaining a large amount of labeled data in medical imaging is laborious and time-consuming, especially for histopathology. However, it is much easier and cheaper to get unlabeled data from whole-slide images (WSIs). Semi-supervised learning (SSL) is an effective way to utilize unlabeled data and alleviate the need for labeled data. For this reason, we proposed a framework that employs an SSL method to accurately detect cancerous regions with a novel annotation method called Minimal Point-Based annotation, and then utilize the predicted results with an innovative hybrid loss to train a classification model for subtyping. The annotator only needs to mark a few points and label them are cancer or not in each WSI. Experiments on three significant subtypes of renal cell carcinoma (RCC) proved that the performance of the classifier trained with the Min-Point annotated dataset is comparable to a classifier trained with the segmentation annotated dataset for cancer region detection. And the subtyping model outperforms a model trained with only diagnostic labels by 12% in terms of f1-score for testing WSIs.
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