Computer aided diagnosis algorithms for digital microscopy

Automatic analysis and information extraction from an image is still a highly chal- lenging research problem in the computer vision area, attempting to describe the image content with computational and mathematical techniques. Moreover the in- formation extracted from the image should be meaningful and as most discrimi- natory as possible, since it will be used to categorize its content according to the analysed problem. In the Medical Imaging domain this issue is even more felt because many important decisions that affect the patient care, depend on the use- fulness of the information extracted from the image. Manage medical image is even more complicated not only due to the importance of the problem, but also because it needs a fair amount of prior medical knowledge to be able to represent with data the visual information to which pathologist refer. Today medical decisions that impact patient care rely on the results of laboratory tests to a greater extent than ever before, due to the marked expansion in the number and complexity of offered tests. These developments promise to improve the care of patients, but the more increase the number and complexity of the tests, the more increases the possibility to misapply and misinterpret the test themselves, leading to inappropriate diagnosis and therapies. Moreover, with the increased number of tests also the amount of data to be analysed increases, forcing pathologists to devote much time to the analysis of the tests themselves rather than to patient care and the prescription of the right therapy, especially considering that most of the tests performed are just check up tests and most of the analysed samples come from healthy patients. Then, a quantitative evaluation of medical images is really essential to overcome uncertainty and subjectivity, but also to greatly reduce the amount of data and the timing for the analysis. In the last few years, many computer assisted diagno- sis systems have been developed, attempting to mimic pathologists by extracting features from the images. Image analysis involves complex algorithms to identify and characterize cells or tissues using image pattern recognition technology. This thesis addresses the main problems associated to the digital microscopy analysis in histology and haematology diagnosis, with the development of algorithms for the extraction of useful information from different digital images, but able to distinguish different biological structures in the images themselves. The proposed methods not only aim to improve the degree of accuracy of the analysis, and reducing time, if used as the only means of diagnoses, but also they can be used as intermediate tools for skimming the number of samples to be analysed directly from the pathologist, or as double check systems to verify the correct results of the automated facilities used today

Computer aided diagnosis algorithms for digital microscopy

Automatic analysis and information extraction from an image is still a highly chal- lenging research problem in the computer vision area, attempting to describe the image content with computational and mathematical techniques. Moreover the in- formation extracted from the image should be meaningful and as most discrimi- natory as possible, since it will be used to categorize its content according to the analysed problem. In the Medical Imaging domain this issue is even more felt because many important decisions that affect the patient care, depend on the use- fulness of the information extracted from the image. Manage medical image is even more complicated not only due to the importance of the problem, but also because it needs a fair amount of prior medical knowledge to be able to represent with data the visual information to which pathologist refer. Today medical decisions that impact patient care rely on the results of laboratory tests to a greater extent than ever before, due to the marked expansion in the number and complexity of offered tests. These developments promise to improve the care of patients, but the more increase the number and complexity of the tests, the more increases the possibility to misapply and misinterpret the test themselves, leading to inappropriate diagnosis and therapies. Moreover, with the increased number of tests also the amount of data to be analysed increases, forcing pathologists to devote much time to the analysis of the tests themselves rather than to patient care and the prescription of the right therapy, especially considering that most of the tests performed are just check up tests and most of the analysed samples come from healthy patients. Then, a quantitative evaluation of medical images is really essential to overcome uncertainty and subjectivity, but also to greatly reduce the amount of data and the timing for the analysis. In the last few years, many computer assisted diagno- sis systems have been developed, attempting to mimic pathologists by extracting features from the images. Image analysis involves complex algorithms to identify and characterize cells or tissues using image pattern recognition technology. This thesis addresses the main problems associated to the digital microscopy analysis in histology and haematology diagnosis, with the development of algorithms for the extraction of useful information from different digital images, but able to distinguish different biological structures in the images themselves. The proposed methods not only aim to improve the degree of accuracy of the analysis, and reducing time, if used as the only means of diagnoses, but also they can be used as intermediate tools for skimming the number of samples to be analysed directly from the pathologist, or as double check systems to verify the correct results of the automated facilities used today

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

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

Automatic Detection and Characterization of Pathological Fluid Regions in Optical Coherence Tomography Images

Programa Oficial de Doutoramento en Computación. 5009V01[Abstract] Intraretinal fluid accumulation is both the common symptom and culprit of the main causes of blindness in developed countries: Age-related Macular Degeneration and Diabetic Macular Edema. For its diagnosis, experts of the domain employ Optical Coherence Tomography images (OCT), providing non-invasive cross-sectional representations of the retinal structures. However, like any medical imaging modality, OCT is influenced by multiple factors that impact its quality and subsequent interpretation. Coupled with the subjectiveness of the human experts, these factors can significantly affect the diagnostic process, treatment and quality of life for the affected individuals (particularly in these pathologies where early detection is crucial). To address these challenges, Computer-Aided Diagnosis (CAD) methodologies are developed, offering a layer of abstraction of the information present in the images. Still, in the particular scenario of these pathological fluid accumulations, the development of these methodologies is specially difficult due to their diffuse nature without defined boundaries. In this thesis, we proposed different CAD methodologies with the objective of helping expert clinicians to better detect and understand these pathologies. Furthermore, we expand the developed methodologies to other medical imaging modalities and conditions, such as macular neovascularizations in OCT Angiographies and COVID-19 diagnosis through the analysis of lung chest radiographs.[Resumen] La acumulación de líquido intrarretiniano es tanto síntoma común como culpable de las principales causas de ceguera en los países desarrollados: la degeneración macular asociada a la edad y el edema macular diabético. Para su diagnóstico, los expertos en el campo emplean imágenes de Tomografía de Coherencia Óptica (OCT), que proporcionan representaciones transversales no invasivas de las estructuras retinianas. Sin embargo, al igual que cualquier modalidad de imagen médica, OCT se ve influenciado por múltiples factores que afectan a su calidad y posterior interpretación. Junto con la subjetividad de los expertos humanos, estos factores pueden afectar significativamente el proceso diagnóstico, tratamiento y calidad de vida de las personas afectadas (particularmente en estas patologías donde una detección temprana es crucial). Para abordar estos desafíos, se desarrollan metodologías de diagnóstico asistido por ordenador (CAD), que ofrecen una capa de abstracción de la información presente en las imágenes. Sin embargo, en el escenario particular de estas acumulaciones patológicas de fluido, el desarrollo de estas metodologías es especialmente difícil debido a su naturaleza difusa, sin bordes definidos. En esta tesis doctoral proponemos diferentes metodologías CAD con el objetivo de ayudar a las personas expertas del dominio a detectar y comprender mejor estas patologías. Además, expandimos las metodologías desarrolladas a otras modalidades de imagen médica y afecciones, como al análisis de neovascularizaciones maculares en Angiografía OCT y al diagnóstico de COVID-19 mediante radiografías torácicas.[Resumo] A acumulación de líquido intrarretiniano é tanto o síntoma común como culpable das principais causas de cegueira nos países desenvolvidos: a dexeneración macular asociada á idade e o edema macular diabético. Para o seu diagnóstico, os expertos no campo empregan imaxes de tomografía de coherencia óptica (OCT), que proporcionan representacións transversais non invasivas das estruturas retinianas. Non obstante, ao igual que calquera modalidade de imaxe médica, a OCT vese influenciada por múltiples factores que afectan a s´ua calidade e a súa posterior interpretación. Xunto coa subxectividade dos expertos humanos, estes factores poden afectar significativamente ao proceso diagn´ostico, ao tratamento e á calidade de vida das persoas afectadas (particularmente nestas patoloxías onde unha detección precoz é crucial). Para abordar estes desafíos, desenvólvense metodoloxías de diagnóstico asistido por ordenador (CAD), que ofrecen unha capa de abstracción da información presente nas imaxes. Non obstante, no escenario particular das acumulacións patolóxicas de líquido, o desenvolvemento destas metodoloxías é especialmente difícil debido a súa natureza difusa, sen bordes definidos. Nesta tese de doutoramento propoñemos diferentes metodoloxías de CAD co obxectivo de axudar ás persoas expertas do campo a detectar e comprender mellor estas patoloxías. Ademais, expandimos as metodoloxías desenvoltas a outras modalidades de imaxe médica e patoloxías, como a an´alise de neovascularizacións maculares en Anxiografía OCT e ao diagnóstico da COVID-19 mediante a análise de radiografías torácicas

The impact of pre- and post-image processing techniques on deep learning frameworks: A comprehensive review for digital pathology image analysis

Recently, deep learning frameworks have rapidly become the main methodology for analyzing medical images. Due to their powerful learning ability and advantages in dealing with complex patterns, deep learning algorithms are ideal for image analysis challenges, particularly in the field of digital pathology. The variety of image analysis tasks in the context of deep learning includes classification (e.g., healthy vs. cancerous tissue), detection (e.g., lymphocytes and mitosis counting), and segmentation (e.g., nuclei and glands segmentation). The majority of recent machine learning methods in digital pathology have a pre- and/or post-processing stage which is integrated with a deep neural network. These stages, based on traditional image processing methods, are employed to make the subsequent classification, detection, or segmentation problem easier to solve. Several studies have shown how the integration of pre- and post-processing methods within a deep learning pipeline can further increase the model's performance when compared to the network by itself. The aim of this review is to provide an overview on the types of methods that are used within deep learning frameworks either to optimally prepare the input (pre-processing) or to improve the results of the network output (post-processing), focusing on digital pathology image analysis. Many of the techniques presented here, especially the post-processing methods, are not limited to digital pathology but can be extended to almost any image analysis field

Gaze-Based Human-Robot Interaction by the Brunswick Model

We present a new paradigm for human-robot interaction based on social signal processing, and in particular on the Brunswick model. Originally, the Brunswick model copes with face-to-face dyadic interaction, assuming that the interactants are communicating through a continuous exchange of non verbal social signals, in addition to the spoken messages. Social signals have to be interpreted, thanks to a proper recognition phase that considers visual and audio information. The Brunswick model allows to quantitatively evaluate the quality of the interaction using statistical tools which measure how effective is the recognition phase. In this paper we cast this theory when one of the interactants is a robot; in this case, the recognition phase performed by the robot and the human have to be revised w.r.t. the original model. The model is applied to Berrick, a recent open-source low-cost robotic head platform, where the gazing is the social signal to be considered