Key environmental stress biomarker candidates for the optimisation of chemotherapy treatment of leukaemia

The impact of fluctuations of environmental parameters such as oxygen and starvation on the evolution of leukaemia is analysed in the current review. These fluctuations may occur within a specific patient (in different organs) or across patients (individual cases of hypoglycaemia and hyperglycaemia). They can be experienced as stress stimuli by the cancerous population, leading to an alteration of cellular growth kinetics, metabolism and further resistance to chemotherapy. Therefore, it is of high importance to elucidate key mechanisms that affect the evolution of leukaemia under stress. Potential stress response mechanisms are discussed in this review. Moreover, appropriate cell biomarker candidates related to the environmental stress response and/or further resistance to chemotherapy are proposed. Quantification of these biomarkers can enable the combination of macroscopic kinetics with microscopic information, which is specific to individual patients and leads to the construction of detailed mathematical models for the optimisation of chemotherapy. Due to their nature, these models will be more accurate and precise (in comparison to available macroscopic/black box models) in the prediction of responses of individual patients to treatment, as they will incorporate microscopic genetic and/or metabolic information which is patient-specific.peer-reviewe

Leukaemia Identification based on Texture Analysis of Microscopic Peripheral Blood Images using Feed-Forward Neural Network

ABSTRACT Leukaemia is very dangerous because it includes liquid tumour that it cannot be seen physically and is difficult to detect. Alternative detection of Leukaemia using microscopy can be processed using a computing system. Leukemia disease can be detected by microscopic examination. Microscopic test results can be processed using machine learning for classification systems. The classification system can be obtained using Feed-Forward Neural Network. Extreme Learning Machine (ELM) is a neural network that has a feedforward structure with a single hidden layer. ELM chooses the input weight and hidden neuron bias at random to minimize training time based on the Moore Penrose Pseudoinverse theory. The classification of Leukaemia is based on microscopic peripheral blood images using ELM. The classification stages consist of pre-processing, feature extraction using GLRLM, and classification using ELM. This system is used to classify Leukaemia into three classes, that is acute lymphoblastic Leukaemia, chronic lymphoblastic Leukaemia, and not Leukaemia. The best results were obtained in ten hidden nodes with an accuracy of 100%, a precision of 100%, a withdrawal of 100%

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

Computer aided analysis of additional chromosome aberrations in Philadelphia chromosome positive acute lymphoblastic leukaemia using a simplified computer readable cytogenetic notation

BACKGROUND: The analysis of complex cytogenetic databases of distinct leukaemia entities may help to detect rare recurring chromosome aberrations, minimal common regions of gains and losses, and also hot spots of genomic rearrangements. The patterns of the karyotype alterations may provide insights into the genetic pathways of disease progression. RESULTS: We developed a simplified computer readable cytogenetic notation (SCCN) by which chromosome findings are normalised at a resolution of 400 bands. Lost or gained chromosomes or chromosome segments are specified in detail, and ranges of chromosome breakpoint assignments are recorded. Software modules were written to summarise the recorded chromosome changes with regard to the respective chromosome involvement. To assess the degree of karyotype alterations the ploidy levels and numbers of numerical and structural changes were recorded separately, and summarised in a complex karyotype aberration score (CKAS). The SCCN and CKAS were used to analyse the extend and the spectrum of additional chromosome aberrations in 94 patients with Philadelphia chromosome positive (Ph-positive) acute lymphoblastic leukemia (ALL) and secondary chromosome anomalies. Dosage changes of chromosomal material represented 92.1% of all additional events. Recurring regions of chromosome losses were identified. Structural rearrangements affecting (peri)centromeric chromosome regions were recorded in 24.6% of the cases. CONCLUSIONS: SCCN and CKAS provide unifying elements between karyotypes and computer processable data formats. They proved to be useful in the investigation of additional chromosome aberrations in Ph-positive ALL, and may represent a step towards full automation of the analysis of large and complex karyotype databases

A Review on Classification of White Blood Cells Using Machine Learning Models

The machine learning (ML) and deep learning (DL) models contribute to exceptional medical image analysis improvement. The models enhance the prediction and improve the accuracy by prediction and classification. It helps the hematologist to diagnose the blood cancer and brain tumor based on calculations and facts. This review focuses on an in-depth analysis of modern techniques applied in the domain of medical image analysis of white blood cell classification. For this review, the methodologies are discussed that have used blood smear images, magnetic resonance imaging (MRI), X-rays, and similar medical imaging domains. The main impact of this review is to present a detailed analysis of machine learning techniques applied for the classification of white blood cells (WBCs). This analysis provides valuable insight, such as the most widely used techniques and best-performing white blood cell classification methods. It was found that in recent decades researchers have been using ML and DL for white blood cell classification, but there are still some challenges. 1) Availability of the dataset is the main challenge, and it could be resolved using data augmentation techniques. 2) Medical training of researchers is recommended to help them understand the structure of white blood cells and select appropriate classification models. 3) Advanced DL networks such as Generative Adversarial Networks, R-CNN, Fast R-CNN, and faster R-CNN can also be used in future techniques.Comment: 23 page

On the Effectiveness of Leukocytes Classification Methods in a Real Application Scenario

Automating the analysis of digital microscopic images to identify the cell sub-types or the presence of illness has assumed a great importance since it aids the laborious manual process of review and diagnosis. In this paper, we have focused on the analysis of white blood cells. They are the body’s main defence against infections and diseases and, therefore, their reliable classification is very important. Current systems for leukocyte analysis are mainly dedicated to: counting, sub-types classification, disease detection or classification. Although these tasks seem very different, they share many steps in the analysis process, especially those dedicated to the detection of cells in blood smears. A very accurate detection step gives accurate results in the classification of white blood cells. Conversely, when detection is not accurate, it can adversely affect classification performance. However, it is very common in real-world applications that work on inaccurate or non-accurate regions. Many problems can affect detection results. They can be related to the quality of the blood smear images, e.g., colour and lighting conditions, absence of standards, or even density and presence of overlapping cells. To this end, we performed an in-depth investigation of the above scenario, simulating the regions produced by detection-based systems. We exploit various image descriptors combined with different classifiers, including CNNs, in order to evaluate which is the most suitable in such a scenario, when performing two different tasks: Classification of WBC subtypes and Leukaemia detection. Experimental results have shown that Convolutional Neural Networks are very robust in such a scenario, outperforming common machine learning techniques combined with hand-crafted descriptors. However, when exploiting appropriate images for model training, even simpler approaches can lead to accurate results in both tasks

Quality of life in children with acute lymphoblastic leukaemia: A systematic review

Quality of life (QOL) in children with acute lymphoblastic leukaemia (ALL) is now considered an important outcome measure of treatment for this disease. The aim of this paper is to systematically review studies on QOL in children during treatment for ALL with consideration to methodological details and quality of studies, empirical findings on QOL as reported by children and parents, and whether children and parents differ in their reports on QOL. Searches were conducted in biomedical, psychological and behavioural science databases. Six papers met inclusion criteria for review: 4 cross-sectional studies and 2 qualitative studies. There was little consistency in how QOL was measured or qualitatively assessed across studies. The quality of most studies was limited by small sample sizes and cross-sectional designs. Children's reports on QOL were represented in 3 studies and discrepancies were found between children's and parent's accounts of QOL. There is a need for ongoing research on QOL in children with ALL that use longitudinal designs, large sample sizes, and child reports of QOL. There is a need for theoretical development of the concept of QOL through concept analysis, grounded theory research and empirical validation of developing theory of QOL. Theoretical development of the concept of QOL will contribute to greater clarification of what is meant by QOL than currently exists which in turn has the potential to advance the methodology of measuring this concept in children

A survey on automated detection and classification of acute leukemia and WBCs in microscopic blood cells

Leukemia (blood cancer) is an unusual spread of White Blood Cells or Leukocytes (WBCs) in the bone marrow and blood. Pathologists can diagnose leukemia by looking at a person's blood sample under a microscope. They identify and categorize leukemia by counting various blood cells and morphological features. This technique is time-consuming for the prediction of leukemia. The pathologist's professional skills and experiences may be affecting this procedure, too. In computer vision, traditional machine learning and deep learning techniques are practical roadmaps that increase the accuracy and speed in diagnosing and classifying medical images such as microscopic blood cells. This paper provides a comprehensive analysis of the detection and classification of acute leukemia and WBCs in the microscopic blood cells. First, we have divided the previous works into six categories based on the output of the models. Then, we describe various steps of detection and classification of acute leukemia and WBCs, including Data Augmentation, Preprocessing, Segmentation, Feature Extraction, Feature Selection (Reduction), Classification, and focus on classification step in the methods. Finally, we divide automated detection and classification of acute leukemia and WBCs into three categories, including traditional, Deep Neural Network (DNN), and mixture (traditional and DNN) methods based on the type of classifier in the classification step and analyze them. The results of this study show that in the diagnosis and classification of acute leukemia and WBCs, the Support Vector Machine (SVM) classifier in traditional machine learning models and Convolutional Neural Network (CNN) classifier in deep learning models have widely employed. The performance metrics of the models that use these classifiers compared to the others model are higher