Meningioma classification using an adaptive discriminant wavelet packet transform

Meningioma subtypes classification is a real world problem from the domain of histological image analysis that requires new methods for its resolution. Computerised histopathology presents a whole new set of problems and introduces new challenges in image classification. High intra-class variation and low inter-class differences in textures is often an issue in histological image analysis problems such as Meningioma subtypes classification. In this thesis, we present an adaptive wavelets based technique that adapts to the variation in the texture of meningioma samples and provides high classification accuracy results. The technique provides a mechanism for attaining an image representation consisting of various spatial frequency resolutions that represent the image and are referred to as subbands. Each subband provides different information pertaining to the texture in the image sample. Our novel method, the Adaptive Discriminant Wavelet Packet Transform (ADWPT), provides a means for selecting the most useful subbands and hence, achieves feature selection. It also provides a mechanism for ranking features based upon the discrimination power of a subband. The more discriminant a subband, the better it is for classification. The results show that high classification accuracies are obtained by selecting subbands with high discrimination power. Moreover, subbands that are more stable i.e. have a higher probability of being selected provide better classification accuracies. Stability and discrimination power have been shown to have a direct relationship with classification accuracy. Hence, ADWPT acquires a subset of subbands that provide a highly discriminant and robust set of features for Meningioma subtype classification. Classification accuracies obtained are greater than 90% for most Meningioma subtypes. Consequently, ADWPT is a robust and adaptive technique which enables it to overcome the issue of high intra-class variation by statistically selecting the most useful subbands for meningioma subtype classification. It overcomes the issue of low inter-class variation by adapting to texture samples and extracting the subbands that are best for differentiating between the various meningioma subtype textures

Locality sensitive deep learning for detection and classification of nuclei in routine colon cancer histology images

Detection and classification of cell nuclei in histopathology images of cancerous tissue stained with the standard hematoxylin and eosin stain is a challenging task due to cellular heterogeneity. Deep learning approaches have been shown to produce encouraging results on histopathology images in various studies. In this paper, we propose a Spatially Constrained Convolutional Neural Network (SC-CNN) to perform nucleus detection. SC-CNN regresses the likelihood of a pixel being the center of a nucleus, where high probability values are spatially constrained to locate in the vicinity of the center of nuclei. For classification of nuclei, we propose a novel Neighboring Ensemble Predictor (NEP) coupled with CNN to more accurately predict the class label of detected cell nuclei. The proposed approaches for detection and classification do not require segmentation of nuclei. We have evaluated them on a large dataset of colorectal adenocarcinoma images, consisting of more than 20,000 annotated nuclei belonging to four different classes. Our results show that the joint detection and classification of the proposed SC-CNN and NEP produces the highest average F1 score as compared to other recently published approaches. Prospectively, the proposed methods could offer benefit to pathology practice in terms of quantitative analysis of tissue constituents in whole-slide images, and could potentially lead to a better understanding of cancer

IMAGE UNDERSTANDING OF MOLAR PREGNANCY BASED ON ANOMALIES DETECTION

Cancer occurs when normal cells grow and multiply without normal control. As the cells multiply, they form an area of abnormal cells, known as a tumour. Many tumours exhibit abnormal chromosomal segregation at cell division. These anomalies play an important role in detecting molar pregnancy cancer. Molar pregnancy, also known as hydatidiform mole, can be categorised into partial (PHM) and complete (CHM) mole, persistent gestational trophoblastic and choriocarcinoma. Hydatidiform moles are most commonly found in women under the age of 17 or over the age of 35. Hydatidiform moles can be detected by morphological and histopathological examination. Even experienced pathologists cannot easily classify between complete and partial hydatidiform moles. However, the distinction between complete and partial hydatidiform moles is important in order to recommend the appropriate treatment method. Therefore, research into molar pregnancy image analysis and understanding is critical. The hypothesis of this research project is that an anomaly detection approach to analyse molar pregnancy images can improve image analysis and classification of normal PHM and CHM villi. The primary aim of this research project is to develop a novel method, based on anomaly detection, to identify and classify anomalous villi in molar pregnancy stained images. The novel method is developed to simulate expert pathologists’ approach in diagnosis of anomalous villi. The knowledge and heuristics elicited from two expert pathologists are combined with the morphological domain knowledge of molar pregnancy, to develop a heuristic multi-neural network architecture designed to classify the villi into their appropriated anomalous types. This study confirmed that a single feature cannot give enough discriminative power for villi classification. Whereas expert pathologists consider the size and shape before textural features, this thesis demonstrated that the textural feature has a higher discriminative power than size and shape. The first heuristic-based multi-neural network, which was based on 15 elicited features, achieved an improved average accuracy of 81.2%, compared to the traditional multi-layer perceptron (80.5%); however, the recall of CHM villi class was still low (64.3%). Two further textural features, which were elicited and added to the second heuristic-based multi-neural network, have improved the average accuracy from 81.2% to 86.1% and the recall of CHM villi class from 64.3% to 73.5%. The precision of the multi-neural network II has also increased from 82.7% to 89.5% for normal villi class, from 81.3% to 84.7% for PHM villi class and from 80.8% to 86% for CHM villi class. To support pathologists to visualise the results of the segmentation, a software tool, Hydatidiform Mole Analysis Tool (HYMAT), was developed compiling the morphological and pathological data for each villus analysis

Mitotic cell detection in H&E stained meningioma histopathology slides

Indiana University-Purdue University Indianapolis (IUPUI)Meningioma represent more than one-third of all primary central nervous system (CNS) tumors, and it can be classified into three grades according to WHO (World Health Organization) in terms of clinical aggressiveness and risk of recurrence. A key component of meningioma grades is the mitotic count, which is defined as quantifying the number of cells in the process of dividing (i.e., undergoing mitosis) at a specific point in time. Currently, mitosis counting is done manually by a pathologist looking at 10 consecutive high-power fields (HPF) on a glass slide under a microscope, which is an extremely laborious and time-consuming process. The goal of this thesis is to investigate the use of computerized methods to automate the detection of mitotic nuclei with limited labeled data. We built computational methods to detect and quantify the histological features of mitotic cells on a whole slides image which mimic the exact process of pathologist workflow. Since we do not have enough training data from meningioma slide, we learned the mitotic cell features through public available breast cancer datasets, and predicted on meingioma slide for accuracy. We use either handcrafted features that capture certain morphological, statistical, or textural attributes of mitoses or features learned with convolutional neural networks (CNN). Hand crafted features are inspired by the domain knowledge, while the data-driven VGG16 models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. Our work on detection of mitotic cells shows 100% recall , 9% precision and 0.17 F1 score. The detection using VGG16 performs with 71% recall, 73% precision, and 0.77 F1 score. Finally, this research of automated image analysis could drastically increase diagnostic efficiency and reduce inter-observer variability and errors in pathology diagnosis, which would allow fewer pathologists to serve more patients while maintaining diagnostic accuracy and precision. And all these methodologies will increasingly transform practice of pathology, allowing it to mature toward a quantitative science

Machine Learning Assisted Digital Pathology

Histopatologiset kudosnäytteet sisältävät valtavan määrän tietoa biologisista mekanismeista, jotka vaikuttavat monien tautien ilmenemiseen ja etenemiseen. Tästä syystä histopatologisten näytteiden arviointi on ollut perustana monien tautien diagnostiikassa vuosikymmenien ajan. Perinteinen histopatologinen arviointi on kuitenkin työläs tehtävä ja lisäksi erittäin altis inhimillisille virheille ja voi siten johtaa virheelliseen tai viivästyneeseen diagnoosiin. Viime vuosien teknologinen kehitys on tuonut patologien käyttöön lasiskannerit ja tiedonhallintajarjestelmät ja sitä myötä mahdollistaneet näytelasien digitoinnin ja käynnistäneet koko patologian työnkulun digitalisaation. Histopatologisten näytteiden saatavuus digitaalisina kuvina on puolestaan mahdollistanut älykkäiden algoritmien ja automatisoitujen laskennallisten kuva-analyysityökalujen kehittämisen diagnostiikan tueksi. Koneoppiminen on tekoälyn osa-alue, joka voidaan määritellä datasta oppimiseksi. Kuva-analyysin sovelluksissa, kuvan pikseliarvot muutetaan kvantitatiiviseksi piirre-esitykseksi jonka pohjalta kuva voidaan muuntaa merkitykselliseksi tiedoksi hyvödyntämällä koneoppimista. Vuosien saatossa koneoppimiseen perustuvan kuva-analyysin menetelmät ovat kehittyneet manuaalisesta piirteidenirroituksesta kohti viimevuosien vallitsevia syväoppimiseen pohjautuvia konvoluutioneuroverkkoja. Koneoppimisen hyödyt histopatologisessa arvioinnissa ovat huomattavat, sillä koneoppiminen mahdollistaa kuvien tulkinnan patologiin verrattavalla tarkkuudella ja siten pystyy merkittävästi parantamaan kliinisen patologian diagnostiikan tarkkuutta, toistettavuutta ja tehokkuutta. Tämä väitöstyö esittelee koneoppimiseen pohjautuvia menetelmiä jotka on kehitetty avustamaan kudosnäytteen histopatologista arviointia, vaihetta joka on merkityksellinen niin kliinisessä diagnostiikassa kuin prekliinisissä tutkimuksissa. Työssä esitellään piirteenirroituksen ja koneoppimisen tehokkuus histopatologiseen arviointiin liittyvissä kuva-analyysitehtävissä kuten kudoksen karakterisoinnissa, sekä rintasyövän etäpesäkkeiden, epiteelikudoksen ja tumien tunnistuksessa. Menetelmien lisäksi tässä väitöstyössä on käsitelty keskeisiä haasteita jotka on huomioitava integroitaessa koneoppimismenetelmiä kliiniseen käyttöön. Ennen kaikkea nämä tutkimukset ovat kuitenkin osoittaneet koneoppimisen mahdollisuudet tulevaisuudessa parantaa patologian kliinisten rutiinitehtävien tehokkuutta ja toistettavuutta sekä diagnostiikan laatua.Histopathological tissue samples contain a vast amount of information on underlying biological mechanisms that contribute to disease manifestation and progression. Therefore, diagnosis from histopathological tissue samples has been the gold standard for decades. However, traditional histopathological assessment is a laborious task and prone to human errors, thereby leading to misdiagnosis or delayed diagnosis. The development of whole slide scanners for digitization of tissue glass slides has initiated the transition to a fully digital pathology workflow that allows scanning, interpretation, and management of digital tissue slides. These advances have been the cornerstone for developing intelligent algorithms and automated computational approaches for histopathological assessment and clinical diagnostics. Machine learning is a subcategory of artificial intelligence and can be defined as a process of learning from data. In image analysis tasks, the raw pixel values are transformed into quantitative feature representations. Based on the image data representation, a machine learning model learns a set of rules that can be used to extract meaningful information and knowledge. Over the years, the field of machine learning based image analysis has developed from manually handcrafting complex features to the recent revolution of deep learning and convolutional neural networks. Histopathological assessment can benefit greatly from the ability of machine learning models to discover patterns and connections from the data. Therefore, machine learning holds great promise to improve the accuracy, reproducibility, and efficiency of clinical diagnostics in the field of digital pathology. This thesis is focused on developing machine learning based methods for assisting in the process of histopathological assessment, which is a significant step in clinical diagnostics as well as in preclinical studies. The studies presented in this thesis show the effectiveness of feature engineering and machine learning in histopathological assessment related tasks, such as; tissue characterisation, metastasis detection, epithelial tissue detection, and nuclei detection. Moreover, the studies presented in this thesis address the key challenges related to variation presented in histopathological data as well as the generalisation problem that need to be considered in order to integrate machine learning approaches into clinical practice. Overall, these studies have demonstrated the potential of machine learning for bringing standardization and reproducibility to the process of histopathological assessment

Texture and Colour in Image Analysis

Research in colour and texture has experienced major changes in the last few years. This book presents some recent advances in the field, specifically in the theory and applications of colour texture analysis. This volume also features benchmarks, comparative evaluations and reviews

Automatic Segmentation of Cells of Different Types in Fluorescence Microscopy Images

Recognition of different cell compartments, types of cells, and their interactions is a critical aspect of quantitative cell biology. This provides a valuable insight for understanding cellular and subcellular interactions and mechanisms of biological processes, such as cancer cell dissemination, organ development and wound healing. Quantitative analysis of cell images is also the mainstay of numerous clinical diagnostic and grading procedures, for example in cancer, immunological, infectious, heart and lung disease. Computer automation of cellular biological samples quantification requires segmenting different cellular and sub-cellular structures in microscopy images. However, automating this problem has proven to be non-trivial, and requires solving multi-class image segmentation tasks that are challenging owing to the high similarity of objects from different classes and irregularly shaped structures. This thesis focuses on the development and application of probabilistic graphical models to multi-class cell segmentation. Graphical models can improve the segmentation accuracy by their ability to exploit prior knowledge and model inter-class dependencies. Directed acyclic graphs, such as trees have been widely used to model top-down statistical dependencies as a prior for improved image segmentation. However, using trees, a few inter-class constraints can be captured. To overcome this limitation, polytree graphical models are proposed in this thesis that capture label proximity relations more naturally compared to tree-based approaches. Polytrees can effectively impose the prior knowledge on the inclusion of different classes by capturing both same-level and across-level dependencies. A novel recursive mechanism based on two-pass message passing is developed to efficiently calculate closed form posteriors of graph nodes on polytrees. Furthermore, since an accurate and sufficiently large ground truth is not always available for training segmentation algorithms, a weakly supervised framework is developed to employ polytrees for multi-class segmentation that reduces the need for training with the aid of modeling the prior knowledge during segmentation. Generating a hierarchical graph for the superpixels in the image, labels of nodes are inferred through a novel efficient message-passing algorithm and the model parameters are optimized with Expectation Maximization (EM). Results of evaluation on the segmentation of simulated data and multiple publicly available fluorescence microscopy datasets indicate the outperformance of the proposed method compared to state-of-the-art. The proposed method has also been assessed in predicting the possible segmentation error and has been shown to outperform trees. This can pave the way to calculate uncertainty measures on the resulting segmentation and guide subsequent segmentation refinement, which can be useful in the development of an interactive segmentation framework