Towards the Point of Care and Noninvasive Classification of Bladder Cancer from Urine Sediment Infrared Spectroscopy. Spectral differentiation of normal, abnormal and cancer patients

Bladder cancer (BC) is the 9th cancer cause of death and one of most cost-intensive in the world. The diagnostic tools are still not at all satisfactory. Herein we evaluated the potential of infrared spectroscopy to detect molecular changes that precede and accompany the carcinogenesis in voided urine sediment. We collected 165 samples from patients being diagnosed for BC and measured them with attenuated total reflectance Fourier transformed infrared spectroscopy (ATR FTIR). Samples were primarily divided into three groups according to cytology that indicated the presence of normal, abnormal and cancer cells. ATR FTIR spectra of sediments were analyzed with the use of partial least square discriminant analysis (PLSDA). The 1800–750 cm− 1 region discriminated the three groups with selectivity and sensitivity values around 68% using cytology as a reference method. These cross-validation values (which were found significant according to a permutation test) were comparable to the sensitivity and specificity values of cytology versus the gold standard (histology). The average spectra of each class and the regression vectors of the PLS-DA indicated that an increased content of carbohydrates and nucleic acids as well as transformations of protein secondary structures were the main discriminators of healthy patients from abnormal and cancer groups. Additionally, we revised the obtained classification according to diagnosis made on histopathological assessment of bladder sections. We finally discuss the potential of the technique to be used as a Point of Care (PoC) testing tool

Classification of squamous cell cervical cytology

Cervical cancer occurs significantly in women in developing countries every day and produces a high number of casualties, with a large economic and social cost. The World Health Organization, in the right against cervical cancer, promotes early detection screening programs by difeerent detection techniques such as conventional cytology (Pap), cytology liquid medium (CML), DNA test Human Papillomavirus (HPV), staining with dilute acetic acid and Lugol's iodine solution. Conventional cytology is the most used technique, being widely accepted, inexpensive, and with quality control mechanisms. The test has shown a sensitivity of 38% to 84% and a specificity of 90% in multiple studies and has been considered as the choice test for screening [14]. The cervical cancer is not a public health problems in developed countries since more than three decades, among others because of implementation of other tests such as the CML which has increased the sensitivity to a figures that vary between 76% and 99 %. This test in particular produces a thin monolayer of cells that are examined. In our countries this technique is really far from being applied because of its high cost. In consequence, the conventional cytology has remained in practice as the only possible examination of the cervix pathology. In this technique, a sample of cells from the transformation zone of the cervix is taken, using a brush or wooden spatula, spread onto a slide and fixed with a preservative solution. This sample is then sent to a laboratory for staining and microscopic examination to determine whether cells are normal or not. This task requires time and expertise for the diagnosis. Attempting to alleviate the work burden from the number of examinations in clinical routine scenario, some researchers have proposed the development of computational tools to detect and classify the cells of the transformation cervix zone. In the present work the transformation zone is firstly characterized using color and texture descriptors defined in the MPEG-7 standard, and the tissue descriptors are used as the input to a bank of binary classifiers, obtaining a precision of 90% and a sensitivity of 83 %. Unlike traditional approaches that extract cell features from previously segmented cells, the present strategy is completely independent of the particular shape. Yet most works in the domain report higher precision rates, the images used in these works for training and evaluation are really different from what is obtained in the cytology laboratories in Colombia. Overall, most of these methods are applied to monolayer techniques and therefore the recognition rates are better from what we found in the present investigation. However, the main aim of the present work was thus to develop a strategy applicable to our real conditions as a pre-screening method, case in which the method should be robust to many random factors that contaminate the image capture. A segmentation strategy is very easily misleaded by all these factor so that our method should use characteristics independently of the segmentation quality, while the reading time is minimized, as well as the intra-observer variability, facilitating thereby real application of such screening tools.Maestrí

Advances in Image Processing, Analysis and Recognition Technology

For many decades, researchers have been trying to make computers’ analysis of images as effective as the system of human vision is. For this purpose, many algorithms and systems have previously been created. The whole process covers various stages, including image processing, representation and recognition. The results of this work can be applied to many computer-assisted areas of everyday life. They improve particular activities and provide handy tools, which are sometimes only for entertainment, but quite often, they significantly increase our safety. In fact, the practical implementation of image processing algorithms is particularly wide. Moreover, the rapid growth of computational complexity and computer efficiency has allowed for the development of more sophisticated and effective algorithms and tools. Although significant progress has been made so far, many issues still remain, resulting in the need for the development of novel approaches

Towards multimodal nonlinear microscopy in clinics

Multimodal nonlinear microscopy combining two photon excited fluorescence (TPEF), second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) represents a promising and powerful tool for biomedical diagnostics. The method enables label-free visualization of morphology and chemical composition of complex tissues as well as disease related changes and is as such as detailed as staining histologic methods. In this work a compact microscope utilizing novel fiber laser sources and a new approach for data analysis based on colocalization have been developed and tested for detecting various disease patterns, e.g., atherosclerosis and brain tumors.Mit Hilfe der nichtlinearen Multikontrast-Mikroskopie basierend auf den Prozessen Zweiphotonenfluoreszenz (TPEF), Frequenzverdopplung (SHG) und kohärente anti-Stokes Raman-Streuung (CARS), können Morphologie, chemische Zusammensetzung sowie krankheitsbedingte Veränderungen komplexer Gewebe label-frei analog zu histologischen Färbungen dargestellt werden. Potentiell eignet sich die Methode daher für die in vivo Bildgebung und könnte die medizinische Diagnostik entscheidend verbessern. Im Rahmen dieser Arbeit wurde ein kompaktes TPEF/SHG/CARS-Forschungsmikroskop unter Verwendung neuer Faserlaserquellen speziell für die Verwendung in der Klinik entwickelt. Dabei wurde erforscht, wie sich der Bildkontrast durch nahinfrarote Laser sowie eine hohe spektrale Auflösung verbessern lässt. Zusätzlich wurde an Methoden der Datenanalyse multispektraler CARS-Daten gearbeitet, um mittels der Kolokalisationsanalyse die Verteilung verschiedener molekularer Marker in komplexen Geweben zu visualisieren. Das Potential für klinische Anwendungen wurde an verschiedenen Krankheitsbildern wie Arteriosklerose und Tumoren des Hirns demonstriert

Automatic Segmentation and Classification of Red and White Blood cells in Thin Blood Smear Slides

In this work we develop a system for automatic detection and classification of cytological images which plays an increasing important role in medical diagnosis. A primary aim of this work is the accurate segmentation of cytological images of blood smears and subsequent feature extraction, along with studying related classification problems such as the identification and counting of peripheral blood smear particles, and classification of white blood cell into types five. Our proposed approach benefits from powerful image processing techniques to perform complete blood count (CBC) without human intervention. The general framework in this blood smear analysis research is as follows. Firstly, a digital blood smear image is de-noised using optimized Bayesian non-local means filter to design a dependable cell counting system that may be used under different image capture conditions. Then an edge preservation technique with Kuwahara filter is used to recover degraded and blurred white blood cell boundaries in blood smear images while reducing the residual negative effect of noise in images. After denoising and edge enhancement, the next step is binarization using combination of Otsu and Niblack to separate the cells and stained background. Cells separation and counting is achieved by granulometry, advanced active contours without edges, and morphological operators with watershed algorithm. Following this is the recognition of different types of white blood cells (WBCs), and also red blood cells (RBCs) segmentation. Using three main types of features: shape, intensity, and texture invariant features in combination with a variety of classifiers is next step. The following features are used in this work: intensity histogram features, invariant moments, the relative area, co-occurrence and run-length matrices, dual tree complex wavelet transform features, Haralick and Tamura features. Next, different statistical approaches involving correlation, distribution and redundancy are used to measure of the dependency between a set of features and to select feature variables on the white blood cell classification. A global sensitivity analysis with random sampling-high dimensional model representation (RS-HDMR) which can deal with independent and dependent input feature variables is used to assess dominate discriminatory power and the reliability of feature which leads to an efficient feature selection. These feature selection results are compared in experiments with branch and bound method and with sequential forward selection (SFS), respectively. This work examines support vector machine (SVM) and Convolutional Neural Networks (LeNet5) in connection with white blood cell classification. Finally, white blood cell classification system is validated in experiments conducted on cytological images of normal poor quality blood smears. These experimental results are also assessed with ground truth manually obtained from medical experts

Automated classification of cancer tissues using multispectral imagery

Automated classification of medical images for colorectal and prostate cancer diagnosis is a crucial tool for improving routine diagnosis decisions. Therefore, in the last few decades, there has been an increasing interest in refining and adapting machine learning algorithms to classify microscopic images of tumour biopsies. Recently, multispectral imagery has received a significant interest from the research community due to the fast-growing development of high-performance computers. This thesis investigates novel algorithms for automatic classification of colorectal and prostate cancer using multispectral imagery in order to propose a system outperforming the state-of-the-art techniques in the field. To achieve this objective, several feature extraction methods based on image texture have been investigated, analysed and evaluated. A novel texture feature for multispectral images is also constructed as an adaptation of the local binary pattern texture feature to multispectral images by expanding the pixels neighbourhood to the spectral dimension. It has the advantage of capturing the multispectral information with a limited feature vector size. This feature has demonstrated improved classification results when compared against traditional texture features. In order to further enhance the systems performance, advanced classification schemes such as bag-of-features - to better capture local information - and stacked generalisation - to select the most discriminative texture features - are explored and evaluated. Finally, the recent years have seen an accelerated and exponential rise of deep learning, boosted by the advances in hardware, and more specifically graphics processing units. Such models have demonstrated excellent results for supervised learning in multiple applications. This observation has motivated the employment in this thesis of deep neural network architectures, namely convolutional neural networks. Experiments were also carried out to evaluate and compare the performance obtained with the features extracted using convolutional neural networks with random initialisation against features extracted with pre-trained models on ImageNet dataset. The analysis of the classication accuracy achieved with deep learning models reveals that the latter outperforms the previously proposed texture extraction methods. In this thesis, the algorithms are assessed using two separate multiclass datasets: the first one consists of prostate tumour multispectral images, and the second contains multispectral images of colorectal tumours. The colorectal dataset was acquired on a wide domain of the light spectrum ranging from the visible to the infrared wavelengths. This dataset was used to demonstrate the improved results produced using infrared light as well as visible light

Point-of-care oral cytology tool for the screening and assessment of potentially malignant oral lesions

BACKGROUND: Effective detection and monitoring of potentially malignant oral lesions (PMOL) are critical to identifying early stage cancer and improving outcomes. In this study, the authors describe cytopathology tools including machine learning algorithms, clinical algorithms, and test reports developed to assist pathologists and clinicians with PMOL evaluation. METHODS: Data were acquired from a multi-site clinical validation study of 999 subjects with PMOLs and oral squamous cell carcinoma (OSCC) using a cytology-on-a-chip approach. A machine learning model was trained to recognize and quantify the distributions of four cell phenotypes. A least absolute shrinkage and selection operator (lasso) logistic regression model was trained to distinguish PMOLs and cancer across a spectrum of histopathologic diagnoses ranging from benign, to increasing grades of oral epithelial dysplasia (OED), to OSCC using demographics, lesion characteristics, and cell phenotypes. Cytopathology software was developed to assist pathologists in reviewing brush cytology test results, including high-content cell analyses, data visualization tools, and results reporting. RESULTS: Cell phenotypes were accurately determined through an automated cytological assay and machine learning approach (99.3% accuracy). Significant differences in cell phenotype distributions across diagnostic categories were found in three phenotypes (Type 1 ‘mature squamous’, Type 2 ‘small round’, and Type 3 ‘leukocytes’). The clinical algorithms resulted in acceptable performance characteristics (AUC = 0.81 for benign vs. mild dysplasia and 0.95 for benign vs. malignancy). Conclusion: These new cytopathology tools represent a practical solution for rapid PMOL assessment with the potential to facilitate screening and longitudinal monitoring in primary, secondary, and tertiary clinical care settings