Automatic recognition of different types of acute leukaemia using peripheral blood cell images

[eng] Clinical pathologists have learned to identify morphological qualitative features to characterise the different normal cells, as well as the abnormal cell types whose presence in peripheral blood is the evidence of serious haematological diseases. A drawback of visual morphological analysis is that is time consuming, requires well-trained personnel and is prone to intra-observer variability, which is particularly true when dealing with blast cells. Indeed, subtle interclass morphological differences exist for leukaemia types, which turns into low specificity scores in the routine screening. They are well-known the difficulties that clinical pathologists have in the discrimination among different blasts and the subjectivity associated with their morphological recognition. The general objective of this thesis is the automatic recognition of different types of blast cells circulating in peripheral blood in acute leukaemia using digital image processing and machine learning techniques. In order to accomplish this objective, this thesis starts with a discrimination among normal mononuclear cells, reactive lymphocytes and three types of leukemic cells using traditional machine learning techniques and hand-crafted features obtained from cell segmentation. In the second part of the thesis, a new predictive system designed with two serially connected convolutional neural networks is developed for the diagnosis of acute leukaemia. This system was proved to distinguish neoplastic (leukaemia) and non-neoplastic (infections) diseases, as well as recognise the leukaemia lineage. Furthermore, it was evaluated for its integration in a real-clinical setting. This thesis also contributes in advancing the state of the art of the automatic recognition of acute leukaemia by providing a more realistic approach which reflects the real-life complexity of acute leukaemia diagnosis

A dataset of microscopic peripheral blood cell images for development of automatic recognition systems

This article makes available a dataset that was used for the development of an automatic recognition system of peripheral blood cell images using convolutional neural networks [1]. The dataset contains a total of 17,092 images of individual normal cells, which were acquired using the analyzer CellaVision DM96 in the Core Laboratory at the Hospital Clinic of Barcelona. The dataset is organized in the following eight groups: neutrophils, eosinophils, basophils, lymphocytes, monocytes, immature granulocytes (promyelocytes, myelocytes, and metamyelocytes), erythroblasts and platelets or thrombocytes. The size of the images is 360¿×¿363 pixels, in format jpg, and they were annotated by expert clinical pathologists. The images were captured from individuals without infection, hematologic or oncologic disease and free of any pharmacologic treatment at the moment of blood collection. This high-quality labelled dataset may be used to train and test machine learning and deep learning models to recognize different types of normal peripheral blood cells. To our knowledge, this is the first publicly available set with large numbers of normal peripheral blood cells, so that it is expected to be a canonical dataset for model benchmarking.Peer ReviewedPostprint (published version

A deep learning pproach for the morphological recognition of reactive lymphocytes in patients with COVID-19 infection

Laboratory medicine plays a fundamental role in the detection, diagnosis and management of COVID-19 infection. Recent observations of the morphology of cells circulating in blood found the presence of particular reactive lymphocytes (COVID-19 RL) in some of the infected patients and demonstrated that it was an indicator of a better prognosis of the disease. Visual morphological analysis is time consuming, requires smear review by expert clinical pathologists, and is prone to subjectivity. This paper presents a convolutional neural network system designed for automatic recognition of COVID-19 RL. It is based on the Xception71 structure and is trained using images of blood cells from real infected patients. An experimental study is carried out with a group of 92 individuals. The input for the system is a set of images selected by the clinical pathologist from the blood smear of a patient. The output is the prediction whether the patient belongs to the group associated with better prognosis of the disease. A threshold is obtained for the classification system to predict that the smear belongs to this group. With this threshold, the experimental test shows excellent performance metrics: 98.3% sensitivity and precision, 97.1% specificity, and 97.8% accuracy. The system does not require costly calculations and can potentially be integrated into clinical practice to assist clinical pathologists in a more objective smear review for early prognosis.Peer ReviewedPostprint (published version

Automatic recognition of different types of acute leukaemia using peripheral blood cell images

Programa de Doctorat en Biomedicina[eng] Clinical pathologists have learned to identify morphological qualitative features to characterise the different normal cells, as well as the abnormal cell types whose presence in peripheral blood is the evidence of serious haematological diseases. A drawback of visual morphological analysis is that is time consuming, requires well-trained personnel and is prone to intra-observer variability, which is particularly true when dealing with blast cells. Indeed, subtle interclass morphological differences exist for leukaemia types, which turns into low specificity scores in the routine screening. They are well-known the difficulties that clinical pathologists have in the discrimination among different blasts and the subjectivity associated with their morphological recognition. The general objective of this thesis is the automatic recognition of different types of blast cells circulating in peripheral blood in acute leukaemia using digital image processing and machine learning techniques. In order to accomplish this objective, this thesis starts with a discrimination among normal mononuclear cells, reactive lymphocytes and three types of leukemic cells using traditional machine learning techniques and hand-crafted features obtained from cell segmentation. In the second part of the thesis, a new predictive system designed with two serially connected convolutional neural networks is developed for the diagnosis of acute leukaemia. This system was proved to distinguish neoplastic (leukaemia) and non-neoplastic (infections) diseases, as well as recognise the leukaemia lineage. Furthermore, it was evaluated for its integration in a real-clinical setting. This thesis also contributes in advancing the state of the art of the automatic recognition of acute leukaemia by providing a more realistic approach which reflects the real-life complexity of acute leukaemia diagnosis

Atypical lymphoid cells circulating in blood in COVID-19 infection: morphology, immunophenotype and prognosis value

Aims Atypical lymphocytes circulating in blood have been reported in COVID-19 patients. This study aims to (1) analyse if patients with reactive lymphocytes (COVID-19 RL) show clinical or biological characteristics related to outcome; (2) develop an automatic system to recognise them in an objective way and (3) study their immunophenotype. Methods Clinical and laboratory findings in 36 COVID-19 patients were compared between those showing COVID-19 RL in blood (18) and those without (18). Blood samples were analysed in Advia2120i and stained with May Grünwald-Giemsa. Digital images were acquired in CellaVisionDM96. Convolutional neural networks (CNNs) were used to accurately recognise COVID-19 RL. Immunophenotypic study was performed throughflow cytometry. Results Neutrophils, D-dimer, procalcitonin, glomerular filtration rate and total protein values were higher in patients without COVID-19 RL (p<0.05) and four of these patients died. Haemoglobin and lymphocyte counts were higher (p<0.02) and no patients died in the group showing COVID-19 RL. COVID-19 RL showed a distinct deep blue cytoplasm with nucleus mostly in eccentric position. Through two sequential CNNs, they were automatically distinguished from normal lymphocytes and classical RL with sensitivity, specificity and overall accuracy values of 90.5%, 99.4% and 98.7%, respectively. Immunophenotypic analysis revealed COVID-19 RL are mostly activated effector memory CD4 and CD8 T cells. Conclusion We found that COVID-19 RL are related to a better evolution and prognosis. They can be detected by morphology in the smear review, being the computerised approach proposed useful to enhance a more objective recognition. Their presence suggests an abundant production of virus-specific T cells, thus explaining the better outcome of patients showing these cells circulating in blood.Peer ReviewedPostprint (published version