Histopathological image analysis : a review

Over the past decade, dramatic increases in computational power and improvement in image analysis algorithms have allowed the development of powerful computer-assisted analytical approaches to radiological data. With the recent advent of whole slide digital scanners, tissue histopathology slides can now be digitized and stored in digital image form. Consequently, digitized tissue histopathology has now become amenable to the application of computerized image analysis and machine learning techniques. Analogous to the role of computer-assisted diagnosis (CAD) algorithms in medical imaging to complement the opinion of a radiologist, CAD algorithms have begun to be developed for disease detection, diagnosis, and prognosis prediction to complement the opinion of the pathologist. In this paper, we review the recent state of the art CAD technology for digitized histopathology. This paper also briefly describes the development and application of novel image analysis technology for a few specific histopathology related problems being pursued in the United States and Europe

Cuantificación de glándulas en imágenes histopatológicas de cáncer gástrico

Automatic detection and quantification of glands in gastric cancer may contribute to objectively measure the lesion severity, to develop strategies for early diagnosis, and most importantly to improve the patient categorization; however, gland quantification is a highly subjective task, prone to error due to the high biopsy traffic and the experience of each expert. The present master’s dissertation is composed by three chapters that carry to an objective identification of glands. In the first chapter of this document we present a new approach for segmentation of glandular nuclei based on nuclear local and contextual (neighborhood) information “NLCI”. A Gradient-BoostedRegression-Tree classifier is trained to distinguish between glandular nuclei and non glandular nuclei. Validation was carried out using 45.702 annotated nuclei from 90 fields of view (patches) extracted from whole slide images of patients diagnosed with gastric cancer. NLCI achieved an accuracy of 0.977 and an F-measure of 0.955, while R-CNN yielded corresponding accuracy and F-measures of 0.923 and 0.719, respectively. In second chapter we presents an entire framework for automatic detection of glands in gastric cancer images. By selecting gland candidates from a binarized version of the hematoxylin channel. Next, the gland’s shape and nuclei are characterized using local features which feed a Random-Cross-validation method classifier trained previously with images manually annotated by an expert. Validation was carried out using a data-set with 1.330 from seven fields of view extracted from patients diagnosed with gastric cancer whole slide images. Results showed an accuracy of 93 % using a linear classifier. Finally, in the third chapter analyzing gland and their glandular nuclei most relevant features, since predict if a patient will survive more than a year after being diagnosed with gastric cancer. A feature selection based on mutual information: criteria of max-dependency, max-relevance, and min-redundancy “mRMR” approach selects those features that correlated better with patient survival. A data set with 668 Fields of View (FoV), 2.076 glandular structures from 14 whole slide images were extracted from patient diagnosed with gastric cancer. Results showed an accuracy of 78.57 % using a QDA Linear & Quadratic Discriminant Analysis was training with Leave-one-out e.g training with thirteen cases and leaving a separate case to validate.La detección y cuantificación automática de las glándulas en el cáncer gástrico puede contribuir a medir objetivamente la gravedad de la lesión, desarrollar estrategias para el diagnóstico precoz y lo que es más importante, mejorar la categorización del paciente; sin embargo, su cuantificación es una tarea altamente subjetiva, propensa a errores debido al alto tráfico de biopsias y a la experiencia de cada experto. La presente disertación de maestría está compuesta por tres capítulos los cuales llevan a la cuantificación objetiva de glándulas. En el primer capítulo del documento se presenta un nuevo enfoque para la segmentación de los núcleos glandulares en base a la información nuclear local y contextual (vecindario). Se entrenó un Gradient-Boosted-Regression-Tree para distinguir entre núcleos glandulares y núcleos no glandulares. La validación se llevó con 45.702 núcleos anotados manualmente de 90 campos de visión (parches) extraídos de imágenes de biopsias completas de pacientes diagnosticados con cáncer gástrico. NLCI logró una precisión de 0.977% y un F-Score de 0.955%, mientras que fast R-CNN arrojó una precisión de 0.923% y un F-Score y 0.719%. En el segundo capítulo se presenta un marco completo para detección automática de glándulas en imágenes de cáncer gástrico. Las glándulas candidatas se seleccionan de una versión binarizada del canal de hematoxilina. A continuación, la forma y los núcleos de las glándulas se caracterizan y se alimenta un clasificador Random Cross Validation, entrenado previamente con imágenes anotadas manualmente por un experto. La validación se realizó en un conjunto de datos con 1.330 parches extraídos de siete biopsias de pacientes diagnosticados con cáncer gástrico. Los resultados mostraron una precisión del 93% utilizando un clasificador lineal. Finalmente, el tercer capítulo analiza las características más relevantes de las glándulas y sus núcleos glandulares, para predecir la sobrevida a un año de un paciente diagnosticado con cáncer gástrico. Una selección de características basada en información mutua: criterios de dependencia máxima, máxima relevancia y mínima redundancia (mRMR) escogen las características correlacionadas con la supervivencia del paciente. Se extrajo un conjunto de datos con 668 campos de visión (FoV), 2.076 estructuras glandulares de 14 imágenes completas de pacientes diagnosticados con cáncer gástrico. Los resultados mostraron una precisión del 76.3% usando un Análisis Discriminante Lineal y Cuadrático (QDA) y un esquema de evaluación entrenando con trece casos y dejando un caso aparte para validar.Magíster en Ingeniería Biomédica. Línea de investigación: Procesamiento de señale

Color and morphological features extraction and nuclei classification in tissue samples of colorectal cancer

Cancer is an important public health problem and the third most leading cause of death in North America. Among the highest impact types of cancer are colorectal, breast, lung, and prostate. This thesis addresses the features extraction by using different artificial intelligence algorithms that provide distinct solutions for the purpose of Computer-AidedDiagnosis (CAD). For example, classification algorithms are employed in identifying histological structures, such as lymphocytes, cancer-cells nuclei and glands, from features like existence, extension or shape. The morphological aspect of these structures indicates the degree of severity of the related disease. In this paper, we use a large dataset of 5000 images to classify eight different tissue types in the case of colorectal cancer. We compare results with another dataset. We perform image segmentation and extract statistical information about the area, perimeter, circularity, eccentricity and solidity of the interest points in the image. Finally, we use and compare four popular machine learning techniques, i.e., Naive Bayes, Random Forest, Support Vector Machine and Multilayer Perceptron to classify and to improve the precision of category assignation. The performance of each algorithm was measured using 3 types of metrics: Precision, recall and F1-Score representing a huge contribution to the existing literature complementing it in a quantitative way. The large number of images has helped us to circumvent the overfitting and reproducibility problems. The main contribution is the use of new characteristics different from those already studied, this work researches about the color and morphological characteristics in the images that may be useful for performing tissue classification in colorectal cancer histology

Histopathological image analysis: a review,”

Abstract-Over the past decade, dramatic increases in computational power and improvement in image analysis algorithms have allowed the development of powerful computer-assisted analytical approaches to radiological data. With the recent advent of whole slide digital scanners, tissue histopathology slides can now be digitized and stored in digital image form. Consequently, digitized tissue histopathology has now become amenable to the application of computerized image analysis and machine learning techniques. Analogous to the role of computer-assisted diagnosis (CAD) algorithms in medical imaging to complement the opinion of a radiologist, CAD algorithms have begun to be developed for disease detection, diagnosis, and prognosis prediction to complement the opinion of the pathologist. In this paper, we review the recent state of the art CAD technology for digitized histopathology. This paper also briefly describes the development and application of novel image analysis technology for a few specific histopathology related problems being pursued in the United States and Europe

Histopathological image classification using salient point patterns

Ankara : The Department of Computer Engineering and the Graduate School of Engineering and Science of Bilkent University, 2011.Thesis (Master's) -- Bilkent University, 2011.Includes bibliographical references leaves 69-79.Over the last decade, computer aided diagnosis (CAD) systems have gained great importance to help pathologists improve the interpretation of histopathological tissue images for cancer detection. These systems offer valuable opportunities to reduce and eliminate the inter- and intra-observer variations in diagnosis, which is very common in the current practice of histopathological examination. Many studies have been dedicated to develop such systems for cancer diagnosis and grading, especially based on textural and structural tissue image analysis. Although the recent textural and structural approaches yield promising results for different types of tissues, they are still unable to make use of the potential biological information carried by different tissue components. However, these tissue components help better represent a tissue, and hence, they help better quantify the tissue changes caused by cancer. This thesis introduces a new textural approach, called Salient Point Patterns (SPP), for the utilization of tissue components in order to represent colon biopsy images. This textural approach first defines a set of salient points that correspond to nuclear, stromal, and luminal components of a colon tissue. Then, it extracts some features around these salient points to quantify the images. Finally, it classifies the tissue samples by using the extracted features. Working with 3236 colon biopsy samples that are taken from 258 different patients, our experiments demonstrate that Salient Point Patterns approach improves the classification accuracy, compared to its counterparts, which do not make use of tissue components in defining their texture descriptors. These experiments also show that different set of features can be used within the SPP approach for better representation of a tissue image.Çığır, CelalM.S

Color graph representation for structural analysis of tissue images

Ankara : The Department of Computer Engineering and the Institute of Engineering and Science of Bilkent University, 2010.Thesis (Master's) -- Bilkent University, 2010.Includes bibliographical references leaves 71-82.Computer aided image analysis tools are becoming increasingly important in automated cancer diagnosis and grading. They have the potential of assisting pathologists in histopathological examination of tissues, which may lead to a considerable amount of subjectivity. These analysis tools help reduce the subjectivity, providing quantitative information about tissues. In literature, it has been proposed to implement such computational tools using different methods that represent a tissue with different set of image features. One of the most commonly used methods is the structural method that represents a tissue quantifying the spatial relationship of its components. Although previous structural methods lead to promising results for different tissue types, they only use the spatial relations of nuclear tissue components without considering the existence of different components in a tissue. However, additional information that could be obtained from other components of the tissue has an importance in better representing the tissue, and thus, in making more reliable decisions. This thesis introduces a novel structural method to quantify histopathological images for automated cancer diagnosis and grading. Unlike the previous structural methods, it proposes to represent a tissue considering the spatial distribution of different tissue components. To this end, it constructs a graph on multiple tissue components and colors its edges depending on the component types of their end points. Subsequently, a new set of structural features is extracted from these “color graphs” and used in the classification of tissues. Experiments conducted on 3236 photomicrographs of colon tissues that are taken from 258 different patients demonstrate that the color graph approach leads to 94.89 percent training accuracy and 88.63 percent test accuracy. Our experiments also show that the introduction of color edges to represent the spatial relationship of different tissue components and the use of graph features defined on these color edges significantly improve the classification accuracy of the previous structural methods.Altunbay, DoğanM.S

Molecular Imaging

The present book gives an exceptional overview of molecular imaging. Practical approach represents the red thread through the whole book, covering at the same time detailed background information that goes very deep into molecular as well as cellular level. Ideas how molecular imaging will develop in the near future present a special delicacy. This should be of special interest as the contributors are members of leading research groups from all over the world

Biospectroscopy towards screening and diagnosis of cancer

Systems biology is an emerging science that combines high throughput investigation techniques to define the dynamic interplay between different biological regulatory systems in response to internal and external cues. Related technologies, genomics, epigenomics, transcriptomics, proteomics, metabolomics and toponomics have been applied to investigate models of carcinogenesis to identify committing initiating events. Vibrational spectroscopy has the potential to play an integral role within systems biology research approaches, as it is able to identify chemical bond alterations within molecules independent of where these molecules reside. Its integration with current “systems biology” methodologies can contribute in the identification of potential biomarkers of carcinogenesis and assist in their incorporation into clinical practice. Breast tissue undergoes cyclical and longitudinal molecular and histological alterations that are influenced by environmental factors. These factors may include diet and lifestyle in addition to parity, lactation and menopausal status and are implicated in carcinogenesis. Breast cancer may appear decades after the initial carcinogenic event. Available research in this area is limited to when early histological changes occur due to the difficulties imposed by the molecular and histological diversity of breast tissue. Vibrational spectroscopy in combination with powerful chemometric techniques has identified spatial and temporal mammary alterations in benign tissue. Prostate cancer is influenced by environmental factors. Its incidence is higher in populations adopting a Westernised lifestyle and diet and has increased over the past generation. This leads to the assumption that prostatic tissue composition may exhibit chronological alterations. Vibrational spectroscopy techniques were applied to matching prostatic tissues with benign prostatic hyperplasia collected from 1983 to 2013. Significant trans-generational segregation was identified. Spectral areas responsible for this segregation pointed towards epigenetic changes. Immunohistochemical studies for DNA methylation and hypomethylation supported these results. Vibrational spectroscopy techniques were also implemented to explore molecular changes between normal ovarian tissue, borderline ovarian tumours and malignant ovarian carcinomas. Different chemometric techniques were applied to discriminate cancers from controls. Similar techniques were able to segregate different types of epithelial ovarian carcinomas. The accurate diagnosis obtained using ATR-FTIR spectroscopy demonstrates its potential for development as an assisting tool for histopathological diagnosis. The endometrial-myometrial junction areas of benign uterine tissues were scrutinised by Synchrotron FTIR and FPA. These techniques in combination with multivariate analysis revealed clear segregation between the functionalis and basalis layers within the uterine crypts. The same techniques illustrated potential areas within these epithelial surfaces where different stem cell types may reside. Targeting the activation/ inactivation of these stem cells may have applications in the diagnosis and treatment of early uterine cancer

Resampling-based Markovian modeling for automated cancer diagnosis

Ankara : The Department of Computer Engineering and the Graduate School of Engineering and Science of Bilkent University, 2011.Thesis (Master's) -- Bilkent University, 2011.Includes bibliographical references leaves 62-69.Correct diagnosis and grading of cancer is very crucial for planning an effective treatment. However, cancer diagnosis on biopsy images involves visual interpretation of a pathologist, which is highly subjective. This subjectivity may, however, lead to selecting suboptimal treatment plans. In order to circumvent this problem, it has been proposed to use automatic diagnosis and grading systems that help decrease the subjectivity levels by providing quantitative measures. However, one major challenge for designing these systems is the existence of high variance observed in the biopsy images due to the nature of biopsies. Thus, for successful classifications of unseen images, these systems should be trained with a large number of labeled images. However, most of the training sets in this domain have limited size of labeled data since it is quite difficult to collect and label histopathological images. In this thesis, we successfully address this issue by presenting a new resampling framework. This framework relies on increasing the generalization capacity of a classifier by augmenting the size and variation in the training set. To this end, we generate multiple sequences from an image, each of which corresponds to a perturbed sample of the image. Each perturbed sample characterizes different parts of the image, and hence, they are slightly different from each other. The use of these perturbed samples for representing the image increases the size and variability of the training set. These samples are modeled with Markov processes which are used to classify unseen image. Working with histopathological tissue images, our experiments demonstrate that the proposed framework is more effective for both larger and smaller training sets compared against other approaches. Additionally, they show that the use of perturbed samples is effective in a voting scheme which boosts the performance of the classifier.Özdemir, ErdemM.S