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

Classification of histological images of thyroid nodules based on a combination of Deep Features and Machine Learning

Background: Thyroid nodules are a prevalent worldwide disease with complex pathological types. They can be classified as either benign or malignant. This paper presents a tool for automatically classifying histological images of thyroid nodules, with a focus on papillary carcinoma and follicular adenoma. Methods: In this work, two pre-trained Convolutional Neural Network (CNN) architectures, VGG16 and VGG19, are used to extract deep features. Then, a principal component analysis was used to reduce the dimensionality of the vectors. Then, three machine learning algorithms (Support Vector Machine, K-Nearest Neighbor, and Random Forest) were used for classification. These investigations were applied to our database collection, Results: The proposed investigations have been applied to our private database collection with a total of 112 histological images. The highest results were obtained by the VGG16 transfer deep feature and the SVM classifier with an accuracy rate equal to 100%

Interpretable methods in cancer diagnostics

Cancer is a hard problem. It is hard for the patients, for the doctors and nurses, and for the researchers working on understanding the disease and finding better treatments for it. The challenges faced by a pathologist diagnosing the disease for a patient is not necessarily the same as the ones faced by cell biologists working on experimental treatments and understanding the fundamentals of cancer. In this thesis we work on different challenges faced by both of the above teams. This thesis first presents methods to improve the analysis of the flow cy- tometry data used frequently in the diagnosis process, specifically for the two subtypes of non-Hodgkin Lymphoma which are our focus: Follicular Lymphoma and Diffuse Large B Cell Lymphoma. With a combination of concepts from graph theory, dynamic programming, and machine learning, we present methods to improve the diagnosis process and the analysis of the abovementioned data. The interpretability of the method helps a pathologist to better understand a patient’s disease, which itself improves their choices for a treatment. In the second part, we focus on the analysis of DNA-methylation and gene expression data, both of which presenting the challenge of being very high dimen- sional yet with a few number of samples comparatively. We present an ensemble model which adapts to different patterns seen in each given data, in order to adapt to noise and batch effects. At the same time, the interpretability of our model helps a pathologist to better find and tune the treatment for the patient: a step further towards personalized medicine.Krebs ist ein schweres Problem. Es ist schwer für die Patienten, für die Ärzte und Krankenschwestern und für die Forscher, die daran arbeiten, die Krankheit zu verstehen und eine bessere Behandlung dafür zu finden. Die Herausforderungen, mit denen ein Pathologe konfrontiert ist, um die Krankheit eines Patienten zu diagnostizieren, müssen nicht die gleichen sein, mit denen Zellbiologen konfrontiert sind, die an experimentellen Behandlungen arbeiten und die Grundlagen von Krebs verstehen. In dieser Arbeit beschäftigen wir uns mit verschiedenen Herausforderungen, denen sich beide oben genannten Teams stellen. In dieser Arbeit werden zunächst Methoden vorgestellt, um die Analyse der im Diagnoseverfahren häufig verwendeten Durchflusszytometriedaten zu verbessern, insbesondere für die beiden Subtypen des Non-Hodgkin-Lymphoms, auf die wir uns konzentrieren: das follikuläre Lymphom und das diffuse großzellige B-Zell-Lymphom. Mit einer Kombination von Konzepten aus Graphentheorie, dynamischer Programmierung und künstliche Intelligenz präsentieren wir Methoden zur Verbesserung des Diagnoseprozesses und der Analyse der oben genannten Daten. Die Interpretierbarkeit der Methode hilft einem Pathologen, die Apatientenkrankheit besser zu verstehen, was wiederum seine Wahlmöglichkeiten für eine Behandlung verbessert. Im zweiten Teil konzentrieren wir uns auf die Analyse von DNA-Methylierungsund Genexpressionsdaten, die beide die Herausforderung darstellen, sehr hochdimensional zu sein, jedoch mit nur wenigen Proben im Vergleich.Wir präsentieren ein Zusammenstellungsmodell, das sich an unterschiedliche Muster anpasst, die in den jeweiligen Daten zu sehen sind, um sich an Rauschen und Batch-Effekte anzupassen. Gleichzeitig hilft die Interpretierbarkeit unseres Modells einem Pathologen, die Behandlung für den Patienten besser zu finden und abzustimmen: ein Schritt weiter in Richtung personalisierter Medizin

Artificial Immune System Implementation for Predicting WM Presence from MYD88 and CXCR4

Waldenstrom’s Macroglobulinemia (WM) is a rare malignancy that affects human blood cells and spreads slowly. The development of WM occurs whenever the blood cells undergo genetic changes. Better therapies can be offered by the healthcare sector to get rid of the symptoms that cannot be cured. Everyone in the healthcare sector is aware that genetic abnormalities cause WM, but they are unsure of what causes the alterations. The risk factors that increase the number of WM's aberrant cells have been found. The greatest risk variables have a fatal impact on humans. The healthcare sector is working to save lives by offering better care. Only when WM is discovered earlier when it is treatable with better care and potent medications, is it very likely. For analysing the healthcare data associated with WM, a number of prior research studies have suggested both standard and unique software models and techniques. However, the accuracy is subpar and inefficient in terms of both time and money. To analyse the genomic dataset and detect Waldenstrom's Macroglobulinemia or its symptoms, this research explored this issue and suggested an Artificial Immune System (AIS) approach. Software written in Python is used to conduct the experiment and validate the findings. by contrasting the trial outcomes with other performance assessment techniques. The analysis reveals that the suggested AIS algorithm works better than the others

Diagnosis of Leukaemia in Blood Slides Based on a Fine-Tuned and Highly Generalisable Deep Learning Model

Leukaemia is a dysfunction that affects the production of white blood cells in the bone marrow. Young cells are abnormally produced, replacing normal blood cells. Consequently, the person suffers problems in transporting oxygen and in fighting infections. This article proposes a convolutional neural network (CNN) named LeukNet that was inspired on convolutional blocks of VGG-16, but with smaller dense layers. To define the LeukNet parameters, we evaluated different CNNs models and fine-tuning methods using 18 image datasets, with different resolution, contrast, colour and texture characteristics. We applied data augmentation operations to expand the training dataset, and the 5-fold cross-validation led to an accuracy of 98.61%. To evaluate the CNNs generalisation ability, we applied a cross-dataset validation technique. The obtained accuracies using cross-dataset experiments on three datasets were 97.04, 82.46 and 70.24%, which overcome the accuracies obtained by current state-of-the-art methods. We conclude that using the most common and deepest CNNs may not be the best choice for applications where the images to be classified differ from those used in pre-training. Additionally, the adopted cross-dataset validation approach proved to be an excellent choice to evaluate the generalisation capability of a model, as it considers the model performance on unseen data, which is paramount for CAD systems. (c) 2021 by the authors. Licensee MDPI, Basel, Switzerland

Machine Learning in the Nuclear Medicine: Part 2-Neural Networks and Clinical Aspects

COPYRIGHT © 2021 by the Society of Nuclear Medicine and Molecular Imaging.This article is the second part in our machine learning series. Part 1 provided a general overview of machine learning in nuclear medicine. Part 2 focuses on neural networks. We start with an example illustrating how neural networks work and a discussion of potential applications. Recognizing that there is a spectrum of applications, we focus on recent publications in the areas of image reconstruction, low-dose PET, disease detection, and models used for diagnosis and outcome prediction. Finally, since the way machine learning algo- rithms are reported in the literature is extremely variable, we conclude with a call to arms regarding the need for standardized reporting of design and outcome metrics and we propose a basic checklist our community might follow going forward

Performance of externally validated machine learning models based on histopathology images for the diagnosis, classification, prognosis, or treatment outcome prediction in female breast cancer: A systematic review

Numerous machine learning (ML) models have been developed for breast cancer using various types of data. Successful external validation (EV) of ML models is important evidence of their generalizability. The aim of this systematic review was to assess the performance of externally validated ML models based on histopathology images for diagnosis, classification, prognosis, or treatment outcome prediction in female breast cancer. A systematic search of MEDLINE, EMBASE, CINAHL, IEEE, MICCAI, and SPIE conferences was performed for studies published between January 2010 and February 2022. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was employed, and the results were narratively described. Of the 2011 non-duplicated citations, 8 journal articles and 2 conference proceedings met inclusion criteria. Three studies externally validated ML models for diagnosis, 4 for classification, 2 for prognosis, and 1 for both classification and prognosis. Most studies used Convolutional Neural Networks and one used logistic regression algorithms. For diagnostic/classification models, the most common performance metrics reported in the EV were accuracy and area under the curve, which were greater than 87% and 90%, respectively, using pathologists' annotations as ground truth. The hazard ratios in the EV of prognostic ML models were between 1.7 (95% CI, 1.2-2.6) and 1.8 (95% CI, 1.3-2.7) to predict distant disease-free survival; 1.91 (95% CI, 1.11-3.29) for recurrence, and between 0.09 (95% CI, 0.01-0.70) and 0.65 (95% CI, 0.43-0.98) for overall survival, using clinical data as ground truth. Despite EV being an important step before the clinical application of a ML model, it hasn't been performed routinely. The large variability in the training/validation datasets, methods, performance metrics, and reported information limited the comparison of the models and the analysis of their results (...