Automatic detection and classification of leukaemia cells

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Today, there is a substantial number of software and research groups that focus on the development of image processing software to extract useful information from medical images, in order to assist and improve patient diagnosis. The work presented in this thesis is centred on processing of images of blood and bone marrow smears of patients suffering from leukaemia, a common type of cancer. In general, cancer is due to aberrant gene expression, which is caused by either mutations or epigenetic changes in DNA. Poor diet and unhealthy lifestyle may trigger or contribute to these changes, although the underlying mechanism is often unknown. Importantly, many cancer types including leukaemia are curable and patient survival and treatment can be improved, subject to prompt diagnosis. In particular, this study focuses on Acute Myeloid Leukaemia (AML), which can be of eight distinct types (M0 to M7), with the main objective to develop a methodology to automatically detect and classify leukaemia cells into one of the above types. The data was collected from the Department of Haematology, Universiti Sains Malaysia, in Malaysia. Three main methods, namely Cellular Automata, Heuristic Search and classification using Neural Networks are facilitated. In the case of Cellular Automata, an improved method based on the 8-neighbourhood and rules were developed to remove noise from images and estimate the radius of the potential blast cells contained in them. The proposed methodology selects the starting points, corresponding to potential blast cells, for the subsequent seeded heuristic search. The Seeded Heuristic employs a new fitness function for blast cell detection. Furthermore, the WEKA software is utilised for classification of blast cells and hence images, into AML subtypes. As a result accuracy of 97.22% was achieved in the classification of blasts into M3 and other AML subtypes. Finally, these algorithms are integrated into an automated system for image processing. In brief, the research presented in this thesis involves the use of advanced computational techniques for processing and classification of medical images, that is, images of blood samples from patients suffering from leukaemia.The Institute of Higher Education of Malaysia and the Universiti Sains Islam Malaysia (USIM)

Automatic normalized digital color staining in the recognition of abnormal blood cells using generative adversarial networks

Background and Objectives: Combining knowledge of clinical pathologists and deep learning models is a growing trend in morphological analysis of cells circulating in blood to add objectivity, accuracy, and speed in diagnosing hematological and non-hematological diseases. However, the variability in staining protocols across different laboratories can affect the color of images and performance of automatic recognition models. The objective of this work is to develop, train and evaluate a new system for the normalization of color staining of peripheral blood cell images, so that it transforms images from different centers to map the color staining of a reference center (RC) while preserving the structural morphological features. Methods: The system has two modules, GAN1 and GAN2. GAN1 uses the PIX2PIX technique to fade original color images to an adaptive gray, while GAN2 transforms them into RGB normalized images. Both GANs have a similar structure, where the generator is a U-NET convolutional neural network with ResNet and the discriminator is a classifier with ResNet34 structure. Digitally stained images were evaluated using GAN metrics and histograms to assess the ability to modify color without altering cell morphology. The system was also evaluated as a pre-processing tool before cells undergo a classification process. For this purpose, a CNN classifier was designed for three classes: abnormal lymphocytes, blasts and reactive lymphocytes. Results: Training of all GANs and the classifier was performed using RC images, while evaluations were conducted using images from four other centers. Classification tests were performed before and after applying the stain normalization system. The overall accuracy reached a similar value around 96% in both cases for the RC images, indicating the neutrality of the normalization model for the reference images. On the contrary, it was a significant improvement in the classification performance when applying the stain normalization to the other centers. Reactive lymphocytes were the most sensitive to stain normalization, with true positive rates (TPR) increasing from 46.3% - 66% for the original images to 81.2% - 97.2% after digital staining. Abnormal lymphocytes TPR ranged from 31.9% - 95.7% with original images to 83% - 100% with digitally stained images. Blast class showed TPR ranges of 90.3% - 94.4% and 94.4% - 100%, for original and stained images, respectively. Conclusions: The proposed GAN-based normalization staining approach improves the performance of classifiers with multicenter data sets by generating digitally stained images with a quality similar to the original images and adaptability to a reference staining standard. The system requires low computation cost and can help improve the performance of automatic recognition models in clinical settings.This work is part of a research project funded by the Ministry of Science and Innovation of Spain, with reference PID2019-104087RB-I00.Peer ReviewedPostprint (published version

Towards Secure and Intelligent Diagnosis: Deep Learning and Blockchain Technology for Computer-Aided Diagnosis Systems

Cancer is the second leading cause of death across the world after cardiovascular disease. The survival rate of patients with cancerous tissue can significantly decrease due to late-stage diagnosis. Nowadays, advancements of whole slide imaging scanners have resulted in a dramatic increase of patient data in the domain of digital pathology. Large-scale histopathology images need to be analyzed promptly for early cancer detection which is critical for improving patient's survival rate and treatment planning. Advances of medical image processing and deep learning methods have facilitated the extraction and analysis of high-level features from histopathological data that could assist in life-critical diagnosis and reduce the considerable healthcare cost associated with cancer. In clinical trials, due to the complexity and large variance of collected image data, developing computer-aided diagnosis systems to support quantitative medical image analysis is an area of active research. The first goal of this research is to automate the classification and segmentation process of cancerous regions in histopathology images of different cancer tissues by developing models using deep learning-based architectures. In this research, a framework with different modules is proposed, including (1) data pre-processing, (2) data augmentation, (3) feature extraction, and (4) deep learning architectures. Four validation studies were designed to conduct this research. (1) differentiating benign and malignant lesions in breast cancer (2) differentiating between immature leukemic blasts and normal cells in leukemia cancer (3) differentiating benign and malignant regions in lung cancer, and (4) differentiating benign and malignant regions in colorectal cancer. Training machine learning models, disease diagnosis, and treatment often requires collecting patients' medical data. Privacy and trusted authenticity concerns make data owners reluctant to share their personal and medical data. Motivated by the advantages of Blockchain technology in healthcare data sharing frameworks, the focus of the second part of this research is to integrate Blockchain technology in computer-aided diagnosis systems to address the problems of managing access control, authentication, provenance, and confidentiality of sensitive medical data. To do so, a hierarchical identity and attribute-based access control mechanism using smart contract and Ethereum Blockchain is proposed to securely process healthcare data without revealing sensitive information to an unauthorized party leveraging the trustworthiness of transactions in a collaborative healthcare environment. The proposed access control mechanism provides a solution to the challenges associated with centralized access control systems and ensures data transparency and traceability for secure data sharing, and data ownership

The Convergence of Human and Artificial Intelligence on Clinical Care - Part I

This edited book contains twelve studies, large and pilots, in five main categories: (i) adaptive imputation to increase the density of clinical data for improving downstream modeling; (ii) machine-learning-empowered diagnosis models; (iii) machine learning models for outcome prediction; (iv) innovative use of AI to improve our understanding of the public view; and (v) understanding of the attitude of providers in trusting insights from AI for complex cases. This collection is an excellent example of how technology can add value in healthcare settings and hints at some of the pressing challenges in the field. Artificial intelligence is gradually becoming a go-to technology in clinical care; therefore, it is important to work collaboratively and to shift from performance-driven outcomes to risk-sensitive model optimization, improved transparency, and better patient representation, to ensure more equitable healthcare for all

Molecular phylogeny of horseshoe crab using mitochondrial Cox1 gene as a benchmark sequence

An effort to assess the utility of 650 bp Cytochrome C oxidase subunit I (DNA barcode) gene in delineating the members horseshoe crabs (Family: xiphosura) with closely related sister taxa was made. A total of 33 sequences were extracted from National Center for Biotechnological Information (NCBI) which include horseshoe crabs, beetles, common crabs and scorpion sequences. Constructed phylogram showed beetles are closely related with horseshoe crabs than common crabs. Scorpion spp were distantly related to xiphosurans. Phylogram and observed genetic distance (GD) date were also revealed that Limulus polyphemus was closely related with Tachypleus tridentatus than with T.gigas. Carcinoscorpius rotundicauda was distantly related with L.polyphemus. The observed mean Genetic Distance (GD) value was higher in 3rd codon position in all the selected group of organisms. Among the horseshoe crabs high GC content was observed in L.polyphemus (38.32%) and lowest was observed in T.tridentatus (32.35%). We conclude that COI sequencing (barcoding) could be used in identifying and delineating evolutionary relatedness with closely related specie