There are various algorithms and methodologies used for automated screening of cervical cancer by segmenting and classifying cervical cancer cells into different categories. This study presents a critical review of different research papers published that integrated AI methods in screening cervical cancer via different approaches analyzed in terms of typical metrics like dataset size, drawbacks, accuracy etc. An attempt has been made to furnish the reader with an insight of Machine Learning algorithms like SVM (Support Vector Machines), GLCM (Gray Level Co-occurrence Matrix), k-NN (k-Nearest Neighbours), MARS (Multivariate Adaptive Regression Splines), CNNs (Convolutional Neural Networks), spatial fuzzy clustering algorithms, PNNs (Probabilistic Neural Networks), Genetic Algorithm, RFT (Random Forest Trees), C5.0, CART (Classification and Regression Trees) and Hierarchical clustering algorithm for feature extraction, cell segmentation and classification. This paper also covers the publicly available datasets related to cervical cancer. It presents a holistic review on the computational methods that have evolved over the period of time, in chronological order in detection of malignant cells.
The quantitative analysis of cellular membranes helps understanding developmental processes at the cellular level. Particularly 3D microscopic image data offers valuable insights into cell dynamics, but error-free automatic segmentation remains challenging due to the huge amount of data generated and strong variations in image intensities. In this paper, we propose a new 3D segmentation approach which combines the discriminative power of convolutional neural networks (CNNs) for preprocessing and investigates the performance of three watershed-based postprocessing strategies (WS), which are well suited to segment object shapes, even when supplied with vague seed and boundary constraints. To leverage the full potential of the watershed algorithm, the multi-instance segmentation problem is initially interpreted as three-class semantic segmentation problem, which in turn is well-suited for the application of CNNs. Using manually annotated 3D confocal microscopy images of Arabidopsis thaliana, we show the superior performance of the proposed method compared to the state of the art.
Automated detection of cervical cancer cells or cell clumps has the potential to significantly reduce error rate and increase productivity in cervical cancer screening. However, most traditional methods rely on the success of accurate cell segmentation and discriminative hand-crafted features extraction. Recently there are emerging deep learning-based methods which train convolutional neural networks (CNN) to classify image patches, but they are computationally expensive. In this paper we propose an efficient CNN-based object detection methods for cervical cancer cells/clumps detection. Specifically, we utilize the state-of-the-art two-stage object detection method, the Faster-RCNN with Feature Pyramid Network (FPN) as the baseline and propose a novel comparison detector to deal with the limited data problem. The key idea is that classify the proposals by comparing with the reference samples of each category in object detection. In addition, we propose to learn the reference samples of the background from data instead of manually choosing them by some heuristic rules. Experimental results show that the proposed Comparison Detector yields significant improvement on the small dataset, achieving a mean Average Precision (mAP) of 26.3% and an Average Recall (AR) of 35.7%, both improving about 20 points compared to the baseline. Moreover, Comparison Detector improved AR by 4.6 points and achieved marginally better performance in terms of mAP compared with baseline model when training on the medium dataset. Our method is promising for the development of automation-assisted cervical cancer screening systems. Code is available at https://github.com/kuku-sichuan/ComparisonDetector.
We propose a new generative adversarial architecture to mitigate imbalance data problem in medical image semantic segmentation where the majority of pixels belongs to a healthy region and few belong to lesion or non-health region. A model trained with imbalanced data tends to bias toward healthy data which is not desired in clinical applications and predicted outputs by these networks have high precision and low sensitivity. We propose a new conditional generative refinement network with three components: a generative, a discriminative, and a refinement network to mitigate unbalanced data problem through ensemble learning. The generative network learns to a segment at the pixel level by getting feedback from the discriminative network according to the true positive and true negative maps. On the other hand, the refinement network learns to predict the false positive and the false negative masks produced by the generative network that has significant value, especially in medical application. The final semantic segmentation masks are then composed by the output of the three networks. The proposed architecture shows state-of-the-art results on LiTS-2017 for liver lesion segmentation, and two microscopic cell segmentation datasets MDA231, PhC-HeLa. We have achieved competitive results on BraTS-2017 for brain tumour segmentation.
Nuclei detection is an important task in the histology domain as it is a main step toward further analysis such as cell counting, cell segmentation, study of cell connections, etc. This is a challenging task due to the complex texture of histology image, variation in shape, and touching cells. To tackle these hurdles, many approaches have been proposed in the literature where deep learning methods stand on top in terms of performance. Hence, in this paper, we propose a novel framework for nuclei detection based on Mixture Density Networks (MDNs). These networks are suitable to map a single input to several possible outputs and we utilize this property to detect multiple seeds in a single image patch. A new modified form of a cost function is proposed for training and handling patches with missing nuclei. The probability maps of the nuclei in the individual patches are next combined to generate the final image-wide result. The experimental results show the state-of-the-art performance on complex colorectal adenocarcinoma dataset.
Every year millions of people die due to disease of Cancer. Due to its invasive nature it is very complex to cure even in primary stages. Hence, only method to survive this disease completely is via forecasting by analyzing the early mutation in cells of the patient biopsy. Cell Segmentation can be used to find cell which have left their nuclei. This enables faster cure and high rate of survival. Cell counting is a hard, yet tedious task that would greatly benefit from automation. To accomplish this task, segmentation of cells need to be accurate. In this paper, we have improved the learning of training data by our network. It can annotate precise masks on test data. we examine the strength of activation functions in medical image segmentation task by improving learning rates by our proposed Carving Technique. Identifying the cells nuclei is the starting point for most analyses, identifying nuclei allows researchers to identify each individual cell in a sample, and by measuring how cells react to various treatments, the researcher can understand the underlying biological processes at work. Experimental results shows the efficiency of the proposed work.
Ki67 is an important biomarker for breast cancer. Classification of positive and negative Ki67 cells in histology slides is a common approach to determine cancer proliferation status. However, there is a lack of generalizable and accurate methods to automate Ki67 scoring in large-scale patient cohorts. In this work, we have employed a novel deep learning technique based on hypercolumn descriptors for cell classification in Ki67 images. Specifically, we developed the Simultaneous Detection and Cell Segmentation (DeepSDCS) network to perform cell segmentation and detection. VGG16 network was used for the training and fine tuning to training data. We extracted the hypercolumn descriptors of each cell to form the vector of activation from specific layers to capture features at different granularity. Features from these layers that correspond to the same pixel were propagated using a stochastic gradient descent optimizer to yield the detection of the nuclei and the final cell segmentations. Subsequently, seeds generated from cell segmentation were propagated to a spatially constrained convolutional neural network for the classification of the cells into stromal, lymphocyte, Ki67-positive cancer cell, and Ki67-negative cancer cell. We validated its accuracy in the context of a large-scale clinical trial of oestrogen-receptor-positive breast cancer. We achieved 99.06% and 89.59% accuracy on two separate test sets of Ki67 stained breast cancer dataset comprising biopsy and whole-slide images.
There is large consent that successful training of deep networks requires many thousand annotated training samples. In this paper, we present a network and training strategy that relies on the strong use of data augmentation to use the available annotated samples more efficiently. The architecture consists of a contracting path to capture context and a symmetric expanding path that enables precise localization. We show that such a network can be trained end-to-end from very few images and outperforms the prior best method (a sliding-window convolutional network) on the ISBI challenge for segmentation of neuronal structures in electron microscopic stacks. Using the same network trained on transmitted light microscopy images (phase contrast and DIC) we won the ISBI cell tracking challenge 2015 in these categories by a large margin. Moreover, the network is fast. Segmentation of a 512x512 image takes less than a second on a recent GPU. The full implementation (based on Caffe) and the trained networks are available at http://lmb.informatik.uni-freiburg.de/people/ronneber/u-net .
Overlapping of cervical cells and poor contrast of cell cytoplasm are the major issues in accurate detection and segmentation of cervical cells. An unsupervised cell segmentation approach is presented here. Cell clump segmentation was carried out using the extended depth of field (EDF) image created from the images of different focal planes. A modified Otsu method with prior class weights is proposed for accurate segmentation of nuclei from the cell clumps. The cell cytoplasm was further segmented from cell clump depending upon the number of nucleus detected in that cell clump. Level set model was used for cytoplasm segmentation.
The progress in imaging techniques have allowed the study of various aspect of cellular mechanisms. To isolate individual cells in live imaging data, we introduce an elegant image segmentation framework that effectively extracts cell boundaries, even in the presence of poor edge details. Our approach works in two stages. First, we estimate pixel interior/border/exterior class probabilities using random ferns. Then, we use an energy minimization framework to compute boundaries whose localization is compliant with the pixel class probabilities. We validate our approach on a manually annotated dataset.
We study the problems of multi-person pose segmentation in natural images and instance segmentation in biological images with crowded cells. We formulate these distinct tasks as integer programs where variables correspond to poses/cells. To optimize, we propose a generic relaxation scheme for solving these combinatorial problems using a column generation formulation where the program for generating a column is solved via exact optimization of very small scale integer programs. This results in efficient exploration of the spaces of poses and cells.
Cell segmentation and tracking allow us to extract a plethora of cell attributes from bacterial time-lapse cell movies, thus promoting computational modeling and simulation of biological processes down to the single-cell level. However, to analyze successfully complex cell movies, imaging multiple interacting bacterial clones as they grow and merge to generate overcrowded bacterial communities with thousands of cells in the field of view, segmentation results should be near perfect to warrant good tracking results. We introduce here a fully automated closed-loop bio-inspired computational strategy that exploits prior knowledge about the expected structure of a colony's lineage tree to locate and correct segmentation errors in analyzed movie frames. We show that this correction strategy is effective, resulting in improved cell tracking and consequently trustworthy deep colony lineage trees. Our image analysis approach has the unique capability to keep tracking cells even after clonal subpopulations merge in the movie. This enables the reconstruction of the complete Forest of Lineage Trees (FLT) representation of evolving multi-clonal bacterial communities. Moreover, the percentage of valid cell trajectories extracted from the image analysis almost doubles after segmentation correction. This plethora of trustworthy data extracted from a complex cell movie analysis enables single-cell analytics as a tool for addressing compelling questions for human health, such as understanding the role of single-cell stochasticity in antibiotics resistance without losing site of the inter-cellular interactions and microenvironment effects that may shape it.
Two successful approaches for the segmentation of biomedical images are (1) the selection of segment candidates from a merge-tree, and (2) the clustering of small superpixels by solving a Multi-Cut problem. In this paper, we introduce a model that unifies both approaches. Our model, the Candidate Multi-Cut (CMC), allows joint selection and clustering of segment candidates from a merge-tree. This way, we overcome the respective limitations of the individual methods: (1) the space of possible segmentations is not constrained to candidates of a merge-tree, and (2) the decision for clustering can be made on candidates larger than superpixels, using features over larger contexts. We solve the optimization problem of selecting and clustering of candidates using an integer linear program. On datasets of 2D light microscopy of cell populations and 3D electron microscopy of neurons, we show that our method generalizes well and generates more accurate segmentations than merge-tree or Multi-Cut methods alone.
Automated segmentation approaches are crucial to quantitatively analyze large-scale 3D microscopy images. Particularly in deep tissue regions, automatic methods still fail to provide error-free segmentations. To improve the segmentation quality throughout imaged samples, we present a new supervoxel-based 3D segmentation approach that outperforms current methods and reduces the manual correction effort. The algorithm consists of gentle preprocessing and a conservative super-voxel generation method followed by supervoxel agglomeration based on local signal properties and a postprocessing step to fix under-segmentation errors using a Convolutional Neural Network. We validate the functionality of the algorithm on manually labeled 3D confocal images of the plant Arabidopis thaliana and compare the results to a state-of-the-art meristem segmentation algorithm.
The quantitative analysis of 3D confocal microscopy images of the shoot apical meristem helps understanding the growth process of some plants. Cell segmentation in these images is crucial for computational plant analysis and many automated methods have been proposed. However, variations in signal intensity across the image mitigate the effectiveness of those approaches with no easy way for user correction. We propose a web-based collaborative 3D image segmentation application, SEGMENT3D, to leverage automatic segmentation results. The image is divided into 3D tiles that can be either segmented interactively from scratch or corrected from a pre-existing segmentation. Individual segmentation results per tile are then automatically merged via consensus analysis and then stitched to complete the segmentation for the entire image stack. SEGMENT3D is a comprehensive application that can be applied to other 3D imaging modalities and general objects. It also provides an easy way to create supervised data to advance segmentation using machine learning models.
Reliable cell segmentation and classification from biomedical images is a crucial step for both scientific research and clinical practice. A major challenge for more robust segmentation and classification methods is the large variations in the size, shape and viewpoint of the cells, combining with the low image quality caused by noise and artifacts. To address this issue, in this work we propose a learning-based, simultaneous cell segmentation and classification method based on the deep U-Net structure with deformable convolution layers. The U-Net architecture for deep learning has been shown to offer a precise localization for image semantic segmentation. Moreover, deformable convolution layer enables the free form deformation of the feature learning process, thus makes the whole network more robust to various cell morphologies and image settings. The proposed method is tested on microscopic red blood cell images from patients with sickle cell disease. The results show that U-Net with deformable convolution achieves the highest accuracy for segmentation and classification, comparing with original U-Net structure.
Computer vision is experiencing an AI renaissance, in which machine learning models are expediting important breakthroughs in academic research and commercial applications. Effectively training these models, however, is not trivial due in part to hyperparameters: user-configured values that control a model's ability to learn from data. Existing hyperparameter optimization methods are highly parallel but make no effort to balance the search across heterogeneous hardware or to prioritize searching high-impact spaces. In this paper, we introduce a framework for massively Scalable Hardware-Aware Distributed Hyperparameter Optimization (SHADHO). Our framework calculates the relative complexity of each search space and monitors performance on the learning task over all trials. These metrics are then used as heuristics to assign hyperparameters to distributed workers based on their hardware. We first demonstrate that our framework achieves double the throughput of a standard distributed hyperparameter optimization framework by optimizing SVM for MNIST using 150 distributed workers. We then conduct model search with SHADHO over the course of one week using 74 GPUs across two compute clusters to optimize U-Net for a cell segmentation task, discovering 515 models that achieve a lower validation loss than standard U-Net.
Cell segmentation in microscopy is a challenging problem, since cells are often asymmetric and densely packed. This becomes particularly challenging for extremely large images, since manual intervention and processing time can make segmentation intractable. In this paper, we present an efficient and highly parallel formulation for symmetric three-dimensional (3D) contour evolution that extends previous work on fast two-dimensional active contours. We provide a formulation for optimization on 3D images, as well as a strategy for accelerating computation on consumer graphics hardware. The proposed software takes advantage of Monte-Carlo sampling schemes in order to speed up convergence and reduce thread divergence. Experimental results show that this method provides superior performance for large 2D and 3D cell segmentation tasks when compared to existing methods on large 3D brain images.
Deep learning based models have had great success in object detection, but the state of the art models have not yet been widely applied to biological image data. We apply for the first time an object detection model previously used on natural images to identify cells and recognize their stages in brightfield microscopy images of malaria-infected blood. Many micro-organisms like malaria parasites are still studied by expert manual inspection and hand counting. This type of object detection task is challenging due to factors like variations in cell shape, density, and color, and uncertainty of some cell classes. In addition, annotated data useful for training is scarce, and the class distribution is inherently highly imbalanced due to the dominance of uninfected red blood cells. We use Faster Region-based Convolutional Neural Network (Faster R-CNN), one of the top performing object detection models in recent years, pre-trained on ImageNet but fine tuned with our data, and compare it to a baseline, which is based on a traditional approach consisting of cell segmentation, extraction of several single-cell features, and classification using random forests. To conduct our initial study, we collect and label a dataset of 1300 fields of view consisting of around 100,000 individual cells. We demonstrate that Faster R-CNN outperforms our baseline and put the results in context of human performance.
Live cell microscopy sequences exhibit complex spatial structures and complicated temporal behaviour, making their analysis a challenging task. Considering cell segmentation problem, which plays a significant role in the analysis, the spatial properties of the data can be captured using Convolutional Neural Networks (CNNs). Recent approaches show promising segmentation results using convolutional encoder-decoders such as the U-Net. Nevertheless, these methods are limited by their inability to incorporate temporal information, that can facilitate segmentation of individual touching cells or of cells that are partially visible. In order to exploit cell dynamics we propose a novel segmentation architecture which integrates Convolutional Long Short Term Memory (C-LSTM) with the U-Net. The network's unique architecture allows it to capture multi-scale, compact, spatio-temporal encoding in the C-LSTMs memory units. The method was evaluated on the Cell Tracking Challenge and achieved state-of-the-art results (1st on Fluo-N2DH-SIM+ and 2nd on DIC-C2DL-HeLa datasets) The code is freely available at: https://github.com/arbellea/LSTM-UNet.git