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

Malaria Parasitic Detection using a New Deep Boosted and Ensemble Learning Framework

Malaria is a potentially fatal plasmodium parasite injected by female anopheles mosquitoes that infect red blood cells and millions worldwide yearly. However, specialists' manual screening in clinical practice is laborious and prone to error. Therefore, a novel Deep Boosted and Ensemble Learning (DBEL) framework, comprising the stacking of new Boosted-BR-STM convolutional neural networks (CNN) and the ensemble ML classifiers, is developed to screen malaria parasite images. The proposed Boosted-BR-STM is based on a new dilated-convolutional block-based split transform merge (STM) and feature-map Squeezing-Boosting (SB) ideas. Moreover, the new STM block uses regional and boundary operations to learn the malaria parasite's homogeneity, heterogeneity, and boundary with patterns. Furthermore, the diverse boosted channels are attained by employing Transfer Learning-based new feature-map SB in STM blocks at the abstract, medium, and conclusion levels to learn minute intensity and texture variation of the parasitic pattern. The proposed DBEL framework implicates the stacking of prominent and diverse boosted channels and provides the generated discriminative features of the developed Boosted-BR-STM to the ensemble of ML classifiers. The proposed framework improves the discrimination ability and generalization of ensemble learning. Moreover, the deep feature spaces of the developed Boosted-BR-STM and customized CNNs are fed into ML classifiers for comparative analysis. The proposed DBEL framework outperforms the existing techniques on the NIH malaria dataset that are enhanced using discrete wavelet transform to enrich feature space. The proposed DBEL framework achieved Accuracy (98.50%), Sensitivity (0.9920), F-score (0.9850), and AUC (0.997), which suggest it to be utilized for malaria parasite screening.Comment: 26 pages, 10 figures, 9 Table

Artificial Intelligence Based Deep Bayesian Neural Network (DBNN) Toward Personalized Treatment of Leukemia with Stem Cells

The dynamic development of computer and software technology in recent years was accompanied by the expansion and widespread implementation of artificial intelligence (AI) based methods in many aspects of human life. A prominent field where rapid progress was observed are high‐throughput methods in biology that generate big amounts of data that need to be processed and analyzed. Therefore, AI methods are more and more applied in the biomedical field, among others for RNA‐protein binding sites prediction, DNA sequence function prediction, protein‐protein interaction prediction, or biomedical image classification. Stem cells are widely used in biomedical research, e.g., leukemia or other disease studies. Our proposed approach of Deep Bayesian Neural Network (DBNN) for the personalized treatment of leukemia cancer has shown a significant tested accuracy for the model. DBNNs used in this study was able to classify images with accuracy exceeding 98.73%. This study depicts that the DBNN can classify cell cultures only based on unstained light microscope images which allow their further use. Therefore, building a bayesian‐based model to great help during commercial cell culturing, and possibly a first step in the process of creating an automated/semiautomated neural network‐based model for classification of good and bad quality cultures when images of such will be available

The State of Applying Artificial Intelligence to Tissue Imaging for Cancer Research and Early Detection

Artificial intelligence represents a new frontier in human medicine that could save more lives and reduce the costs, thereby increasing accessibility. As a consequence, the rate of advancement of AI in cancer medical imaging and more particularly tissue pathology has exploded, opening it to ethical and technical questions that could impede its adoption into existing systems. In order to chart the path of AI in its application to cancer tissue imaging, we review current work and identify how it can improve cancer pathology diagnostics and research. In this review, we identify 5 core tasks that models are developed for, including regression, classification, segmentation, generation, and compression tasks. We address the benefits and challenges that such methods face, and how they can be adapted for use in cancer prevention and treatment. The studies looked at in this paper represent the beginning of this field and future experiments will build on the foundations that we highlight

Analysis of Signal Decomposition and Stain Separation methods for biomedical applications

Nowadays, the biomedical signal processing and classification and medical image interpretation play an essential role in the detection and diagnosis of several human diseases. The problem of high variability and heterogeneity of information, which is extracted from digital data, can be addressed with signal decomposition and stain separation techniques which can be useful approaches to highlight hidden patterns or rhythms in biological signals and specific cellular structures in histological color images, respectively. This thesis work can be divided into two macro-sections. In the first part (Part I), a novel cascaded RNN model based on long short-term memory (LSTM) blocks is presented with the aim to classify sleep stages automatically. A general workflow based on single-channel EEG signals is developed to enhance the low performance in staging N1 sleep without reducing the performances in the other sleep stages (i.e. Wake, N2, N3 and REM). In the same context, several signal decomposition techniques and time-frequency representations are deployed for the analysis of EEG signals. All extracted features are analyzed by using a novel correlation-based timestep feature selection and finally the selected features are fed to a bidirectional RNN model. In the second part (Part II), a fully automated method named SCAN (Stain Color Adaptive Normalization) is proposed for the separation and normalization of staining in digital pathology. This normalization system allows to standardize digitally, automatically and in a few seconds, the color intensity of a tissue slide with respect to that of a target image, in order to improve the pathologist’s diagnosis and increase the accuracy of computer-assisted diagnosis (CAD) systems. Multiscale evaluation and multi-tissue comparison are performed for assessing the robustness of the proposed method. In addition, a stain normalization based on a novel mathematical technique, named ICD (Inverse Color Deconvolution) is developed for immunohistochemical (IHC) staining in histopathological images. In conclusion, the proposed techniques achieve satisfactory results compared to state-of-the-art methods in the same research field. The workflow proposed in this thesis work and the developed algorithms can be employed for the analysis and interpretation of other biomedical signals and for digital medical image analysis

Differently stained whole slide image registration technique with landmark validation

Abstract. One of the most significant features in digital pathology is to compare and fuse successive differently stained tissue sections, also called slides, visually. Doing so, aligning different images to a common frame, ground truth, is required. Current sample scanning tools enable to create images full of informative layers of digitalized tissues, stored with a high resolution into whole slide images. However, there are a limited amount of automatic alignment tools handling large images precisely in acceptable processing time. The idea of this study is to propose a deep learning solution for histopathology image registration. The main focus is on the understanding of landmark validation and the impact of stain augmentation on differently stained histopathology images. Also, the developed registration method is compared with the state-of-the-art algorithms which utilize whole slide images in the field of digital pathology. There are previous studies about histopathology, digital pathology, whole slide imaging and image registration, color staining, data augmentation, and deep learning that are referenced in this study. The goal is to develop a learning-based registration framework specifically for high-resolution histopathology image registration. Different whole slide tissue sample images are used with a resolution of up to 40x magnification. The images are organized into sets of consecutive, differently dyed sections, and the aim is to register the images based on only the visible tissue and ignore the background. Significant structures in the tissue are marked with landmarks. The quality measurements include, for example, the relative target registration error, structural similarity index metric, visual evaluation, landmark-based evaluation, matching points, and image details. These results are comparable and can be used also in the future research and in development of new tools. Moreover, the results are expected to show how the theory and practice are combined in whole slide image registration challenges. DeepHistReg algorithm will be studied to better understand the development of stain color feature augmentation-based image registration tool of this study. Matlab and Aperio ImageScope are the tools to annotate and validate the image, and Python is used to develop the algorithm of this new registration tool. As cancer is globally a serious disease regardless of age or lifestyle, it is important to find ways to develop the systems experts can use while working with patients’ data. There is still a lot to improve in the field of digital pathology and this study is one step toward it.Eri menetelmin värjättyjen virtuaalinäytelasien rekisteröintitekniikka kiintopisteiden validointia hyödyntäen. Tiivistelmä. Yksi tärkeimmistä digitaalipatologian ominaisuuksista on verrata ja fuusioida peräkkäisiä eri menetelmin värjättyjä kudosleikkeitä toisiinsa visuaalisesti. Tällöin keskenään lähes identtiset kuvat kohdistetaan samaan yhteiseen kehykseen, niin sanottuun pohjatotuuteen. Nykyiset näytteiden skannaustyökalut mahdollistavat sellaisten kuvien luonnin, jotka ovat täynnä kerroksittaista tietoa digitalisoiduista näytteistä, tallennettuna erittäin korkean resoluution virtuaalisiin näytelaseihin. Tällä hetkellä on olemassa kuitenkin vain kourallinen automaattisia työkaluja, jotka kykenevät käsittelemään näin valtavia kuvatiedostoja tarkasti hyväksytyin aikarajoin. Tämän työn tarkoituksena on syväoppimista hyväksikäyttäen löytää ratkaisu histopatologisten kuvien rekisteröintiin. Tärkeimpänä osa-alueena on ymmärtää kiintopisteiden validoinnin periaatteet sekä eri väriaineiden augmentoinnin vaikutus. Lisäksi tässä työssä kehitettyä rekisteröintialgoritmia tullaan vertailemaan muihin kirjallisuudessa esitettyihin algoritmeihin, jotka myös hyödyntävät virtuaalinäytelaseja digitaalipatologian saralla. Kirjallisessa osiossa tullaan siteeraamaan aiempia tutkimuksia muun muassa seuraavista aihealueista: histopatologia, digitaalipatologia, virtuaalinäytelasi, kuvantaminen ja rekisteröinti, näytteen värjäys, data-augmentointi sekä syväoppiminen. Tavoitteena on kehittää oppimispohjainen rekisteröintikehys erityisesti korkearesoluutioisille digitalisoiduille histopatologisille kuville. Erilaisissa näytekuvissa tullaan käyttämään jopa 40-kertaista suurennosta. Kuvat kudoksista on järjestetty eri menetelmin värjättyihin peräkkäisiin kuvasarjoihin ja tämän työn päämääränä on rekisteröidä kuvat pohjautuen ainoastaan kudosten näkyviin osuuksiin, jättäen kuvien tausta huomioimatta. Kudosten merkittävimmät rakenteet on merkattu niin sanotuin kiintopistein. Työn laatumittauksina käytetään arvoja, kuten kohteen suhteellinen rekisteröintivirhe (rTRE), rakenteellisen samankaltaisuuindeksin mittari (SSIM), sekä visuaalista arviointia, kiintopisteisiin pohjautuvaa arviointia, yhteensopivuuskohtia, ja kuvatiedoston yksityiskohtia. Nämä arvot ovat verrattavissa myös tulevissa tutkimuksissa ja samaisia arvoja voidaan käyttää uusia työkaluja kehiteltäessä. DeepHistReg metodi toimii pohjana tässä työssä kehitettävälle näytteen värjäyksen parantamiseen pohjautuvalle rekisteröintityökalulle. Matlab ja Aperio ImageScope ovat ohjelmistoja, joita tullaan hyödyntämään tässä työssä kuvien merkitsemiseen ja validointiin. Ohjelmointikielenä käytetään Pythonia. Syöpä on maailmanlaajuisesti vakava sairaus, joka ei katso ikää eikä elämäntyyliä. Siksi on tärkeää löytää uusia keinoja kehittää työkaluja, joita asiantuntijat voivat hyödyntää jokapäiväisessä työssään potilastietojen käsittelyssä. Digitaalipatologian osa-alueella on vielä paljon innovoitavaa ja tämä työ on yksi askel eteenpäin taistelussa syöpäsairauksia vastaan

Improvements in Digital Holographic Microscopy

The Ph.D. dissertation consists of developing a series of innovative computational methods for improving digital holographic microscopy (DHM). DHM systems are widely used in quantitative phase imaging for studying micrometer-size biological and non-biological samples. As any imaging technique, DHM systems have limitations that reduce their applicability. Current limitations in DHM systems are: i) the number of holograms (more than three holograms) required in slightly off-axis DHM systems to reconstruct the object phase information without applying complex computational algorithms; ii) the lack of an automatic and robust computation algorithm to compensate for the interference angle and reconstruct the object phase information without phase distortions in off-axis DHM systems operating in telecentric and image plane conditions; iii) the necessity of an automatic computational algorithm to simultaneously compensate for the interference angle and numerically focus out-of-focus holograms on reconstructing the object phase information without phase distortions in off-axis DHM systems operating in telecentric regime; iv) the deficiency of reconstructing phase images without phase distortions at video-rate speed in off-axis DHM operating in telecentric regime, and image plane conditions; v) the lack of an open-source library for any DHM optical configuration; and, finally, vi) the tradeoff between speckle contrast and spatial resolution existing in current computational strategies to reduce the speckle contrast. This Ph.D. dissertation is motivated to overcome or at least reduce the six limitations mentioned above. Each chapter of this dissertation presents and discusses a novel computational method from the theoretical and experimental point of view to address each of these limitations

Image Processing Methods for Automatic in-vitro Morphology Analysis

The study of male infertility has become a priority for biologists and researchers in the last decades as a consequence of the declining birth rates. This problem has also become a major public health with economic and psychosocial consequences. Analysis of human sperm cells, for instance, is widely used in investigations related to male infertility and assisted conception. Sperm samples are usually analysed by health professionals using microscope devices following a manual process to count and describe their morphology. Nevertheless, this practice is prone to errors and time consuming. This thesis proposes a novel framework based on image processing and machine learning methods to automate the analysis of sperm cells. The proposed method presented an average accuracy performance of 96.4% classify automatically sperm cells in three classes: normal, abnormal and non sperm cell. Performance results have been obtained in challenging conditions: presence of uneven illumination, unwanted noise and blurring caused by the focus drift and occlusion of objects as a result of the overlapping of sperm cells, among others. The object of interest, sperm cells, captured in the images used in this research did not receive any staining or fixation treatment prior to their capture. A novel and robust methodology based on deep neural learning is developed as part of the automatic feature selection prior to the classification. Also, video and image database of sperm samples was produced at the Andrology laboratory of the University of Sheffield as part of this work. The database was used to validate the proposed framework for the segmentation and classification of in-vitro cells