Novel chromatin texture features for the classification of Pap smears

This paper presents a set of novel structural texture features for quantifying nuclear chromatin patterns in cells on a conventional Pap smear. The features are derived from an initial segmentation of the chromatin into bloblike texture primitives. The results of a comprehensive feature selection experiment, including the set of proposed structural texture features and a range of different cytology features drawn from the literature, show that two of the four top ranking features are structural texture features. They also show that a combination of structural and conventional features yields a classification performance of 0.954±0.019 (AUC±SE) for the discrimination of normal (NILM) and abnormal (LSIL and HSIL) slides. The results of a second classification experiment, using only normal-appearing cells from both normal and abnormal slides, demonstrates that a single structural texture feature measuring chromatin margination yields a classification performance of 0.815±0.019. Overall the results demonstrate the efficacy of the proposed structural approach and that it is possible to detect malignancy associated changes (MACs) in Papanicoloau stain

A Detection Method of Ectocervical Cell Nuclei for Pap test Images, Based on Adaptive Thresholds and Local Derivatives

Cervical cancer is one of the main causes of death by disease worldwide. In Peru, it holds the first place in frequency and represents 8% of deaths caused by sickness. To detect the disease in the early stages, one of the most used screening tests is the cervix Papanicolaou test. Currently, digital images are increasingly being used to improve Pap test efficiency. This work develops an algorithm based on adaptive thresholds, which will be used in Pap smear assisted quality control software. The first stage of the method is a pre-processing step, in which noise and background removal is done. Next, a block is segmented for each one of the points selected as not background, and a local threshold per block is calculated to search for cell nuclei. If a nucleus is detected, an artifact rejection follows, where only cell nuclei and inflammatory cells are left for the doctors to interpret. The method was validated with a set of 55 images containing 2317 cells. The algorithm successfully recognized 92.3% of the total nuclei in all images collected.Revisón por pare

A Deep Learning based Pipeline for Efficient Oral Cancer Screening on Whole Slide Images

Oral cancer incidence is rapidly increasing worldwide. The most important determinant factor in cancer survival is early diagnosis. To facilitate large scale screening, we propose a fully automated pipeline for oral cancer detection on whole slide cytology images. The pipeline consists of fully convolutional regression-based nucleus detection, followed by per-cell focus selection, and CNN based classification. Our novel focus selection step provides fast per-cell focus decisions at human-level accuracy. We demonstrate that the pipeline provides efficient cancer classification of whole slide cytology images, improving over previous results both in terms of accuracy and feasibility. The complete source code is available at https://github.com/MIDA-group/OralScreen.Comment: Accepted to ICIAR 202

Otimização de descritores usados nos estudos de cambios associadas à malignidade em imagens digitais de células cervicais

Orientadores: Marco Antonio Garcia de Carvalho, Guilherme Palermo CoelhoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de TecnologiaResumo: O Câncer de Colo de Útero (CCU) é um problema de saúde coletiva em todo o mundo, nesse sentido foram feitos grandes avanços para sua detecção e prevenção. Apesar dos esforços feitos pelos países da América Latina para reduzir os indicadores de mortes por essa doença, eles ainda não são suficientes em comparação com o progresso de outros países europeus.Uma das razões, é que os sistemas de saúde pública em vários países da América têm limitações importantes em seus programas de acompanhamento e prevenção.O vírus do papanicolau está associado a 95 % dos cânceres cervicais, embora as instituições de saúde pública em todo o mundo invistam esforços técnicos, humanos e econômicos para reduzir o impacto da CCU em suas comunidades. Desde 1960, são realizadas pesquisas a respeito ao exame do Papanicolau, considerado este como um dos mecanismos mais utilizados pelo mundo para controlar e diagnosticar esta doença. Alterações Associadas à Malignidade (MAC), são pequenas alterações na morfologia e textura da cromatina, predizendo possíveis lesões malignas associadas ao CCU, tornando-se uma investigação interessante na aplicação do exame do panicolau. A identificação de MAC¿s em imagens de células cervicais é um problema accessível a possíveis investigações, devido às complexidades da identificação visual de estruturas nucleares. A partir das técnicas de Processamento Digital de Imagens (PDI), tem se conseguido grandes avanços, especialmente na obtenção de 400 descritores para o estudo de MAC's, no entanto a pequena quantidade de imagens focadas no estudo MAC, assim como a limitação técnica do equipamento e poucos profissionais que trabalham nesses estudos limitam o progresso nesta área. Esta tese tem como objetivo, otimizar descritores propostos na literatura para o estudo do MAC utilizando PDI. Para atingir este objetivo, foi criado em conjunto com a Fundação Universitária de Ciências para a Saúde da Colômbia (FUCS), um Data set de imagens de células cervicais que possibilitará o estudo de MAC's. Para adquirir imagens para o estudo, foram digitalizadas 6 folhas de pacientes com diferentes patologias que foram diagnosticadas e marcadas por uma cito-técnica especializada. As imagens foram pré-processadas empregando filtros espaciais e núcleos segmentados usando o algoritmo k-means e watershed. Os canais de cor foram separados pela sua contribuição de hematoxilina e corante Orange G6 dos núcleos segmentados; se extraíram 800 descritores morfológicos, de textura, densidade óptica e iluminação dos núcleos para sua posterior classificação. Contribuímos com a criação de um conjunto de dados para o estudo do MAC em imagens de CCU de exames de citologia convencional. Comparamos três classificadores supervisionados, treinados com 795 descritores, 412 descritores, 200 descritores e 962 instâncias. Calculamos e ordenamos os descritores extraídos pela informação obtida de cada um deles. Com um grupo de descritores, a precisão da classificação é 95,3 %. A segmentação dos núcleos mostrou uma precisão de 85,6 %. A otimização dos descritores foi de 4,3% melhor que a dos descritores propostos pela literatura, sendo composta por 30% de descritores de textura, 27% de descritores morfológicos, 11,5% de descritores de densidade óptica e 17% de descritores associados à concordância de níveis de cinzaAbstract: Cervical cancer (CCU) is a collective health problem worldwide, in that sense great advances have been made for its detection and prevention. Despite the efforts made by Latin American countries to reduce the indicators of deaths from this disease, they are still not sufficient compared to the progress of other European countries. One of the reasons is that the public health systems of several countries in the Americas present important limitations in their monitoring and prevention programs. The Human Papilloma Virus is associated with 95% of cervical cancers. Public health institutions around the world invest technical, human, and economic efforts to lessen the impact of the CCU on their communities. The mechanism most used by the world to control and diagnose this disease is the examination of the Human Papilloma. Research on this test has been conducted since 1960. The Malignancy Associated Changes MAC, are slight alterations in the morphology and texture of chromatin predicting possible malignant lesions associated to CCU, becoming one of the promising researches to be applied in the examination of the human papilloma. The identification of MAC's in cervical cell images is an open problem, due to the complexities of visual identification of nuclear structures. From Digital Image Processing (DIP) techniques great advances have been made especially in obtaining 400 descriptors for the study of MAC's, however the small amount of images focused on MAC's study, as well as the technical limitation of the equipment and few professionals who worked to these studies has limited progress in this area. The objective of this thesis is to optimize the descriptors proposed in the literature for the study of MAC using DIP. In order to achieve this objective, a set of cervical cell images was created for the study of MAC's, in conjunction with the Fundación Universitaria de Ciencias para la Salud-Colombia (FUCS). With the purpose of acquiring images for the study, 6 slides of patients with different pathologies were digitalized, which were diagnosed and labeled by a specialized cyto-technique. The images were pre-processed using spatial filters and segmented nuclei using the k-means and watershed algorithm. The color channels were separated by contribution of Hematoxylin and Orange G6 dye from the segmented nuclei; 800 morphological, texture, optical density and illumination descriptors were extracted from the nuclei for later classification. We contributed with the creation of a Data Set for the study of MAC in CCU images of conventional cytology examinations. We compared three supervised classifiers with 795 descriptors, 412 descriptors, 200 descriptors and 962 instances. We calculated and sorted the extracted descriptors by the information gain of each one of them. The optimization of the descriptors was 4.3% better than the descriptors proposed in the literature, consisting of 30% texture descriptors, 27% morphological descriptors, 11.5% optical density descriptors and 17% descriptors associated with the agreement of gray levelsDoutoradoSistemas de Informação e ComunicaçãoDoutor em TecnologiaCAPE

Medical image segmentation using edge-based active contours.

The main purpose of image segmentation using active contours is to extract the object of interest in images based on textural or boundary information. Active contour methods have been widely used in image segmentation applications due to their good boundary detection accuracy. In the context of medical image segmentation, weak edges and inhomogeneities remain important issues that may limit the accuracy of any segmentation method formulated using active contour models. This thesis develops new methods for segmentation of medical images based on the active contour models. Three different approaches are pursued: The first chapter proposes a novel external force that integrates gradient vector flow (GVF) field forces and balloon forces based on a weighting factor computed according to local image features. The proposed external force reduces noise sensitivity, improves performance over weak edges and allows initialization with a single manually selected point. The next chapter proposes a level set method that is based on the minimization of an objective energy functional whose energy terms are weighted according to their relative importance in detecting boundaries. This relative importance is computed based on local edge features collected from the adjacent region inside and outside of the evolving contour. The local edge features employed are the edge intensity and the degree of alignment between the images gradient vector flow field and the evolving contours normal. Finally, chapter 5 presents a framework that is capable of segmenting the cytoplasm of each individual cell and can address the problem of segmenting overlapping cervical cells using edge-based active contours. The main goal of our methodology is to provide significantly fully segmented cells with high accuracy segmentation results. All of the proposed methods are then evaluated for segmentation of various regions in real MRI and CT slices, X-ray images and cervical cell images. Evaluation results show that the proposed method leads to more accurate boundary detection results than other edge-based active contour methods (snake and level-set), particularly around weak edges

Deep Learning in Medical Image Analysis

The accelerating power of deep learning in diagnosing diseases will empower physicians and speed up decision making in clinical environments. Applications of modern medical instruments and digitalization of medical care have generated enormous amounts of medical images in recent years. In this big data arena, new deep learning methods and computational models for efficient data processing, analysis, and modeling of the generated data are crucially important for clinical applications and understanding the underlying biological process. This book presents and highlights novel algorithms, architectures, techniques, and applications of deep learning for medical image analysis

Evaluation of PD-L1 expression in various formalin-fixed paraffin embedded tumour tissue samples using SP263, SP142 and QR1 antibody clones

Background & objectives: Cancer cells can avoid immune destruction through the inhibitory ligand PD-L1. PD-1 is a surface cell receptor, part of the immunoglobulin family. Its ligand PD-L1 is expressed by tumour cells and stromal tumour infltrating lymphocytes (TIL). Methods: Forty-four cancer cases were included in this study (24 triple-negative breast cancers (TNBC), 10 non-small cell lung cancer (NSCLC) and 10 malignant melanoma cases). Three clones of monoclonal primary antibodies were compared: QR1 (Quartett), SP 142 and SP263 (Ventana). For visualization, ultraView Universal DAB Detection Kit from Ventana was used on an automated platform for immunohistochemical staining Ventana BenchMark GX. Results: Comparing the sensitivity of two different clones on same tissue samples from TNBC, we found that the QR1 clone gave higher percentage of positive cells than clone SP142, but there was no statistically significant difference. Comparing the sensitivity of two different clones on same tissue samples from malignant melanoma, the SP263 clone gave higher percentage of positive cells than the QR1 clone, but again the difference was not statistically significant. Comparing the sensitivity of two different clones on same tissue samples from NSCLC, we found higher percentage of positive cells using the QR1 clone in comparison with the SP142 clone, but once again, the difference was not statistically significant. Conclusion: The three different antibody clones from two manufacturers Ventana and Quartett, gave comparable results with no statistically significant difference in staining intensity/ percentage of positive tumour and/or immune cells. Therefore, different PD-L1 clones from different manufacturers can potentially be used to evaluate the PD- L1 status in different tumour tissues. Due to the serious implications of the PD-L1 analysis in further treatment decisions for cancer patients, every antibody clone, staining protocol and evaluation process should be carefully and meticulously validated

A study of the molecular pathology of ductal carcinoma in situ and invasive ductal carcinoma of the breast.

The biological validity of the histopathological classification of ductal carcinoma in situ (DCIS) of the breast was evaluated in this study by correlating the three histopathological grades of DCIS to immunohistochemical expression of Ki67, p53, cerbB-2, markers of poor prognosis in invasive ductal carcinoma (IDC) and also to bcl2 and ER, markers of good prognosis in invasive breast cancer. DCIS grades correlated positively to Ki67, p53, cerbB-2 and negatively to bcl2 and ER, suggesting validity of the classification. The incidence of bax protein expression was determined immunohistochemically in DCIS and IDC. It did not correlate to histopathological grades of DCIS or IDC. The relationships of bax protein to the above mentioned biological markers were also determined in DCIS and IDC. Furthermore, the expression of bax, bcl2, Ki67, ER, p53 and cerbB-2 within DCIS grades was compared with the expression of these markers within IDC grades. The DCIS grades were determined subjectively as well as objectively by means of computer assisted image analysis with significant correlation found between subjective and objective measures. Image analysis was also used to determine percentage of positive cells per case for the nuclear stains (Ki67, ER, p53). Immunohistochemically positive p53 cases were analysed for p53 mutation by polymerase chain reaction (PCR) and subsequent DNA sequencing to compare the incidence of p53 mutation in DCIS to that of IDC. Biochemical changes within tissue may either initiate disease or occur as the result of the disease process and these changes can be studied by both Fourier transform infrared (FTIR) and FT-Raman spectroscopic techniques. FTIR and FT-Raman were employed to distinguish the DCIS and IDC grades. It has the potential to distinguish between DCIS grades, between IDC grades and also between DCIS and IDC as whole groups. The implications of the obtained data for the understanding of the molecular biology of DCIS of the breast and IDC are discussed and future investigations to further elucidate the molecular and cellular mechanisms involved are proposed