Automatic segmentation of overlapping cervical smear cells based on local distinctive features and guided shape deformation

Automated segmentation of cells from cervical smears poses great challenge to biomedical image analysis because of the noisy and complex background, poor cytoplasmic contrast and the presence of fuzzy and overlapping cells. In this paper, we propose an automated segmentation method for the nucleus and cytoplasm in a cluster of cervical cells based on distinctive local features and guided sparse shape deformation. Our proposed approach is performed in two stages: segmentation of nuclei and cellular clusters, and segmentation of overlapping cytoplasm. In the rst stage, a set of local discriminative shape and appearance cues of image superpixels is incorporated and classi ed by the Support Vector Machine (SVM) to segment the image into nuclei, cellular clusters, and background. In the second stage, a robust shape deformation framework is proposed, based on Sparse Coding (SC) theory and guided by representative shape features, to construct the cytoplasmic shape of each overlapping cell. Then, the obtained shape is re ned by the Distance Regularized Level Set Evolution (DRLSE) model. We evaluated our approach using the ISBI 2014 challenge dataset, which has 135 synthetic cell images for a total of 810 cells. Our results show that our approach outperformed existing approaches in segmenting overlapping cells and obtaining accurate nuclear boundaries. Keywords: overlapping cervical smear cells, feature extraction, sparse coding, shape deformation, distance regularized level set

Recent Advances in Morphological Cell Image Analysis

This paper summarizes the recent advances in image processing methods for morphological cell analysis. The topic of morphological analysis has received much attention with the increasing demands in both bioinformatics and biomedical applications. Among many factors that affect the diagnosis of a disease, morphological cell analysis and statistics have made great contributions to results and effects for a doctor. Morphological cell analysis finds the cellar shape, cellar regularity, classification, statistics, diagnosis, and so forth. In the last 20 years, about 1000 publications have reported the use of morphological cell analysis in biomedical research. Relevant solutions encompass a rather wide application area, such as cell clumps segmentation, morphological characteristics extraction, 3D reconstruction, abnormal cells identification, and statistical analysis. These reports are summarized in this paper to enable easy referral to suitable methods for practical solutions. Representative contributions and future research trends are also addressed

A Comprehensive Overview of Computational Nuclei Segmentation Methods in Digital Pathology

In the cancer diagnosis pipeline, digital pathology plays an instrumental role in the identification, staging, and grading of malignant areas on biopsy tissue specimens. High resolution histology images are subject to high variance in appearance, sourcing either from the acquisition devices or the H\&E staining process. Nuclei segmentation is an important task, as it detects the nuclei cells over background tissue and gives rise to the topology, size, and count of nuclei which are determinant factors for cancer detection. Yet, it is a fairly time consuming task for pathologists, with reportedly high subjectivity. Computer Aided Diagnosis (CAD) tools empowered by modern Artificial Intelligence (AI) models enable the automation of nuclei segmentation. This can reduce the subjectivity in analysis and reading time. This paper provides an extensive review, beginning from earlier works use traditional image processing techniques and reaching up to modern approaches following the Deep Learning (DL) paradigm. Our review also focuses on the weak supervision aspect of the problem, motivated by the fact that annotated data is scarce. At the end, the advantages of different models and types of supervision are thoroughly discussed. Furthermore, we try to extrapolate and envision how future research lines will potentially be, so as to minimize the need for labeled data while maintaining high performance. Future methods should emphasize efficient and explainable models with a transparent underlying process so that physicians can trust their output.Comment: 47 pages, 27 figures, 9 table

Computerized cancer malignancy grading of fine needle aspirates

According to the World Health Organization, breast cancer is a leading cause of death among middle-aged women. Precise diagnosis and correct treatment significantly reduces the high number of deaths caused by breast cancer. Being successful in the treatment strictly relies on the diagnosis. Specifically, the accuracy of the diagnosis and the stage at which a cancer was diagnosed. Precise and early diagnosis has a major impact on the survival rate, which indicates how many patients will live after the treatment. For many years researchers in medical and computer science fields have been working together to find the approach for precise diagnosis. For this thesis, precise diagnosis means finding a cancer at as early a stage as possible by developing new computer aided diagnostic tools. These tools differ depending on the type of cancer and the type of the examination that is used for diagnosis. This work concentrates on cytological images of breast cancer that are produced during fine needle aspiration biopsy examination. This kind of examination allows pathologists to estimate the malignancy of the cancer with very high accuracy. Malignancy estimation is very important when assessing a patients survival rate and the type of treatment. To achieve precise malignancy estimation, a classification framework is presented. This framework is able to classify breast cancer malignancy into two malignancy classes and is based on features calculated according to the Bloom-Richardson grading scheme. This scheme is commonly used by pathologists when grading breast cancer tissue. In Bloom-Richardson scheme two types of features are assessed depending on the magnification. Low magnification images are used for examining the dispersion of the cells in the image while the high magnification images are used for precise analysis of the cells' nuclear features. In this thesis, different types of segmentation algorithms were compared to estimate the algorithm that allows for relatively fast and accurate nuclear segmentation. Based on that segmentation a set of 34 features was extracted for further malignancy classification. For classification purposes 6 different classifiers were compared. From all of the tests a set of the best preforming features were chosen. The presented system is able to classify images of fine needle aspiration biopsy slides with high accurac

Computer-aided Cytological Grading Systems for Fine Needle Aspiration Biopsies of Breast Cancer

According to the American Cancer Society, breast cancer is the world's most commonly diagnosed and deadliest form of cancer in women. A major determinant of the survival rate in breast cancer patients are the accuracy and speed of the malignancy grade determination. This thesis considers the classification problem related to determining the grade of a malignant tumor accurately and efficiently. A Fine Needle Aspiration (FNA) biopsy is a key mechanism for breast cancer diagnosis as well as for assigning grades to malignant cases. Carrying out a manual examination of FNA demands substantial work from the pathologist which may result in delays, human errors, and consequently lead to misclassified grades. In this context, the most common grading system for microscopic imaging for breast cancer is the Bloom and Richardson (BR) histological grading system which is based on the evaluation of tissues and cells. BR is not directly applicable to FNA biopsy slides due to distortion of tissue and even cell structures on the cytological slides. Therefore, in this thesis, to grade FNA images of breast cancer, instead of the BR grading scheme, six known cytological grading schemes, three newly proposed cytological grading schemes, and five grading systems based on convolutional neural networks were proposed to automatically determine the malignancy grade of breast cancer. First, considering traditional Machine Learning methods, six cytological grading systems (CA-CGSs) based on six cytological schemes used by pathologists for FNA biopsies of breast cancer were proposed to grade tumors. Each system was built using the cytological criteria as proposed in the original CGSs. The six considered cytological grading schemes in this thesis were Fisher's modification of Black's nuclear grading, Mouriquand's grading, Robinson's grading, Taniguchi et al's, Khan et al's and Howell's modification in mitosis count criteria. To fulfill this task, different sets of handcrafted features using customized image processing algorithms were extracted for classification purpose. The proposed systems were able efficiently to classify FNA slides into G2 (moderately malignant) or G3 (highly malignant) cases using traditional machine learning algorithms. Additionally, three new cytological grading systems were proposed by augmenting three of the original CGSs by adding the low magnification features. However, the systems were not sensitive enough with regards to G3 cases due to the low number of available data samples. Therefore, a data balancing was performed to improve the sensitivity for G3 cases. Consequently, in the second objective of this work, data sampling and RUSBoost methods were applied to the datasets to adjust the class distribution and boost the sensitivity performance of the proposed systems. This enabled a sensitivity improvement of up to 30% which highlights the significance of class balancing in the task of malignancy grading of breast cancer. Additionally, due to the considerable time and efforts required for handcrafted features-based cytological grading systems in order to achieve efficient feature engineering results, a deep learning (DL) approach was proposed to avoid the aforementioned challenges without compromising the grading accuracy. Thus, in this thesis, five different pre-trained convolutional neural network (CNN) models, namely GoogleNet Inception-v3, AlexNet, ResNet18, ResNet50, and ResNet101, combined with different techniques to deal with unbalanced data, were used to develop automated computer-aided cytological malignancy grading systems (CNN-CMGSs). According to the obtained results, the proposed CNN-CMGS based on GoogleNet Inception-v3 combined with the oversampling method provides the best accuracy performance for the problem at hand. The results demonstrated that the proposed CGSs are highly correlated since they share some of the cytological criteria. Further, the overall accuracy of the CGSs is roughly the same and overall, the handcrafted features-based CGSs performed best even in the absence of class distribution rebalancing. Overall, for case classification, the best results were obtained for computer-aided CGSs based on the modified Khan et al.’s and Robinson’s schemes with accuracies of 97.77% and 97.28%, respectively. Meanwhile, for patient classification, the overall best results were obtained for computer-aided CGSs based on the modified Khan et al.’s and modified Fisher's schemes with accuracies of 96.50% and 95.71%, respectively. These results surpass previously reported results in the literature for computer-aided CGS based on BR histologic grading. Moreover, in clinical practice, Robinson’s typically has the best diagnostic accuracy with the highest reported experimental accuracy rate of 90%. Thus, the obtained results demonstrate that computer-aided breast cancer cytological grading systems using FNA can potentially achieve accuracy rates comparable to the more invasive histopathological BR-method

Medical Image Segmentation by Deep Convolutional Neural Networks

Medical image segmentation is a fundamental and critical step for medical image analysis. Due to the complexity and diversity of medical images, the segmentation of medical images continues to be a challenging problem. Recently, deep learning techniques, especially Convolution Neural Networks (CNNs) have received extensive research and achieve great success in many vision tasks. Specifically, with the advent of Fully Convolutional Networks (FCNs), automatic medical image segmentation based on FCNs is a promising research field. This thesis focuses on two medical image segmentation tasks: lung segmentation in chest X-ray images and nuclei segmentation in histopathological images. For the lung segmentation task, we investigate several FCNs that have been successful in semantic and medical image segmentation. We evaluate the performance of these different FCNs on three publicly available chest X-ray image datasets. For the nuclei segmentation task, since the challenges of this task are difficulty in segmenting the small, overlapping and touching nuclei, and limited ability of generalization to nuclei in different organs and tissue types, we propose a novel nuclei segmentation approach based on a two-stage learning framework and Deep Layer Aggregation (DLA). We convert the original binary segmentation task into a two-step task by adding nuclei-boundary prediction (3-classes) as an intermediate step. To solve our two-step task, we design a two-stage learning framework by stacking two U-Nets. The first stage estimates nuclei and their coarse boundaries while the second stage outputs the final fine-grained segmentation map. Furthermore, we also extend the U-Nets with DLA by iteratively merging features across different levels. We evaluate our proposed method on two public diverse nuclei datasets. The experimental results show that our proposed approach outperforms many standard segmentation architectures and recently proposed nuclei segmentation methods, and can be easily generalized across different cell types in various organs