Nuclear segmentation in digital microscopic tissue images can enable extraction of high-quality features for nuclear morphometrics and other analysis in computational pathology. Conventional image processing techniques, such as Otsu thresholding and watershed segmentation, do not work effectively on challenging cases, such as chromatin-sparse and crowded nuclei. In contrast, machine learning-based segmentation can generalize across various nuclear appearances. However, training machine learning algorithms requires data sets of images, in which a vast number of nuclei have been annotated. Publicly accessible and annotated data sets, along with widely agreed upon metrics to compare techniques, have catalyzed tremendous innovation and progress on other image classification problems, particularly in object recognition. Inspired by their success, we introduce a large publicly accessible data set of hematoxylin and eosin (H&E)-stained tissue images with more than 21000 painstakingly annotated nuclear boundaries, whose quality was validated by a medical doctor. Because our data set is taken from multiple hospitals and includes a diversity of nuclear appearances from several patients, disease states, and organs, techniques trained on it are likely to generalize well and work right out-of-the-box on other H&E-stained images. We also propose a new metric to evaluate nuclear segmentation results that penalizes object- and pixel-level errors in a unified manner, unlike previous metrics that penalize only one type of error. We also propose a segmentation technique based on deep learning that lays a special emphasis on identifying the nuclear boundaries, including those between the touching or overlapping nuclei, and works well on a diverse set of test images.

Generalized nucleus segmentation techniques can contribute greatly to reducing the time to develop and validate visual biomarkers for new digital pathology datasets. We summarize the results of MoNuSeg 2018 Challenge whose objective was to develop generalizable nuclei segmentation techniques in digital pathology. The challenge was an official satellite event of the MICCAI 2018 conference in which 32 teams with more than 80 participants from geographically diverse institutes participated. Contestants were given a training set with 30 images from seven organs with annotations of 21,623 individual nuclei. A test dataset with 14 images taken from seven organs, including two organs that did not appear in the training set was released without annotations. Entries were evaluated based on average aggregated Jaccard index (AJI) on the test set to prioritize accurate instance segmentation as opposed to mere semantic segmentation. More than half the teams that completed the challenge outperformed a previous baseline [1]. Among the trends observed that contributed to increased accuracy were the use of color normalization as well as heavy data augmentation. Additionally, fully convolutional networks inspired by variants of U-Net [2], FCN [3], and Mask- RCNN [4] were popularly used, typically based on ResNet [5] or VGG [6] base architectures. Watershed segmentation on predicted semantic segmentation maps was a popular post-processing strategy. Several of the top techniques compared favorably to an individual human annotator and can be used with confidence for nuclear morphometrics.

Existing deep learning technologies generally learn the features of chest X-ray data generated by Generative Adversarial Networks (GAN) to diagnose COVID-19 pneumonia. However, the above methods have a critical challenge: data privacy. GAN will leak the semantic information of the training data which can be used to reconstruct the training samples by attackers, thereby this method will leak the privacy of the patient. Furthermore, for this reason, that is the limitation of the training data sample, different hospitals jointly train the model through data sharing, which will also cause privacy leakage. To solve this problem, we adopt the Federated Learning (FL) framework, a new technique being used to protect data privacy. Under the FL framework and Differentially Private thinking, we propose a Federated Differentially Private Generative Adversarial Network (FedDPGAN) to detect COVID-19 pneumonia for sustainable smart cities. Specifically, we use DP-GAN to privately generate diverse patient data in which differential privacy technology is introduced to make sure the privacy protection of the semantic information of the training dataset. Furthermore, we leverage FL to allow hospitals to collaboratively train COVID-19 models without sharing the original data. Under Independent and Identically Distributed (IID) and non-IID settings, the evaluation of the proposed model is on three types of chest X-ray (CXR)images dataset (COVID-19, normal, and normal pneumonia). A large number of truthful reports make the verification of our model can effectively diagnose COVID-19 without compromising privacy.

Detecting various types of cells in and aroundthe tumor matrix holds a special significance in characterizing the tumor micro-environment for cancer prognostication and research. Automating the tasks of detecting, segmenting, and classifying nuclei can free up the pathologists' time for higher value tasks and reduce errors due to fatigue and subjectivity. To encourage the computer vision research community to develop and test algorithms for these tasks, we prepared a large and diverse dataset of nucleus boundary annotations and class labels. The dataset has over 46,000 nuclei from 37 hospitals, 71 patients, four organs, and four nucleus types. We also organized a challenge around this dataset as a satellite event at the International Symposium on Biomedical Imaging (ISBI) in April 2020. The challenge saw a wide participation from across the world, and the top methods were able to match inter-human concordance for the challenge metric. In this paper, we summarize the dataset and the key findings of the challenge, including the commonalities and differences between the methods developed by various participants. We have released the MoNuSAC2020 dataset to the public.

Context:Color normalization techniques for histology have not been empirically tested for their utility for computational pathology pipelines.Aims:We compared two contemporary techniques for achieving a common intermediate goal – epithelial-stromal classification.Settings and Design:Expert-annotated regions of epithelium and stroma were treated as ground truth for comparing classifiers on original and color-normalized images.Materials and Methods:Epithelial and stromal regions were annotated on thirty diverse-appearing H and E stained prostate cancer tissue microarray cores. Corresponding sets of thirty images each were generated using the two color normalization techniques. Color metrics were compared for original and color-normalized images. Separate epithelial-stromal classifiers were trained and compared on test images. Main analyses were conducted using a multiresolution segmentation (MRS) approach; comparative analyses using two other classification approaches (convolutional neural network [CNN], Wndchrm) were also performed.Statistical Analysis:For the main MRS method, which relied on classification of super-pixels, the number of variables used was reduced using backward elimination without compromising accuracy, and test - area under the curves (AUCs) were compared for original and normalized images. For CNN and Wndchrm, pixel classification test-AUCs were compared.Results:Khan method reduced color saturation while Vahadane reduced hue variance. Super-pixel-level test-AUC for MRS was 0.010–0.025 (95% confidence interval limits ± 0.004) higher for the two normalized image sets compared to the original in the 10–80 variable range. Improvement in pixel classification accuracy was also observed for CNN and Wndchrm for color-normalized images.Conclusions:Color normalization can give a small incremental benefit when a super-pixel-based classification method is used with features that perform implicit color normalization while the gain is higher for patch-based classification methods for classifying epithelium versus stroma.

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