Methods for Analysing Endothelial Cell Shape and Behaviour in Relation to the Focal Nature of Atherosclerosis

The aim of this thesis is to develop automated methods for the analysis of the spatial patterns, and the functional behaviour of endothelial cells, viewed under microscopy, with applications to the understanding of atherosclerosis. Initially, a radial search approach to segmentation was attempted in order to trace the cell and nuclei boundaries using a maximum likelihood algorithm; it was found inadequate to detect the weak cell boundaries present in the available data. A parametric cell shape model was then introduced to fit an equivalent ellipse to the cell boundary by matching phase-invariant orientation fields of the image and a candidate cell shape. This approach succeeded on good quality images, but failed on images with weak cell boundaries. Finally, a support vector machines based method, relying on a rich set of visual features, and a small but high quality training dataset, was found to work well on large numbers of cells even in the presence of strong intensity variations and imaging noise. Using the segmentation results, several standard shear-stress dependent parameters of cell morphology were studied, and evidence for similar behaviour in some cell shape parameters was obtained in in-vivo cells and their nuclei. Nuclear and cell orientations around immature and mature aortas were broadly similar, suggesting that the pattern of flow direction near the wall stayed approximately constant with age. The relation was less strong for the cell and nuclear length-to-width ratios. Two novel shape analysis approaches were attempted to find other properties of cell shape which could be used to annotate or characterise patterns, since a wide variability in cell and nuclear shapes was observed which did not appear to fit the standard parameterisations. Although no firm conclusions can yet be drawn, the work lays the foundation for future studies of cell morphology. To draw inferences about patterns in the functional response of cells to flow, which may play a role in the progression of disease, single-cell analysis was performed using calcium sensitive florescence probes. Calcium transient rates were found to change with flow, but more importantly, local patterns of synchronisation in multi-cellular groups were discernable and appear to change with flow. The patterns suggest a new functional mechanism in flow-mediation of cell-cell calcium signalling

Dual-wavelength thulium fluoride fiber laser based on SMF-TMSIF-SMF interferometer as potential source for microwave generationin 100-GHz region

A dual-wavelength thulium-doped fluoride fiber (TDFF) laser is presented. The generation of the TDFF laser is achieved with the incorporation of a single modemultimode- single mode (SMS) interferometer in the laser cavity. The simple SMS interferometer is fabricated using the combination of two-mode step index fiber and single-mode fiber. With this proposed design, as many as eight stable laser lines are experimentally demonstrated. Moreover, when a tunable bandpass filter is inserted in the laser cavity, a dual-wavelength TDFF laser can be achieved in a 1.5-μm region. By heterodyning the dual-wavelength laser, simulation results suggest that the generated microwave signals can be tuned from 105.678 to 106.524 GHz with a constant step of �0.14 GHz. The presented photonics-based microwave generation method could provide alternative solution for 5G signal sources in 100-GHz region

The detection and classification of blast cell in Leukaemia Acute Promyelocytic Leukaemia (AML M3) blood using simulated annealing and neural networks

This paper was delivered at AIME 2011: 13th Conference on Artifical Intelligence in Medicine.This paper presents a method for the detection and classification of blast cells in M3 with others sub-types using simulated annealing and neural networks. In this paper, we increased our test result from 10 images to 20 images. We performed Hill Climbing, Simulated Annealing and Genetic Algorithms for detecting the blast cells. As a result, simulated annealing is the “best” heuristic search for detecting the leukaemia cells. From the detection, we performed features extraction on the blast cells and we classifying based on M3 and other sub-types using neural networks. We received convincing result which has targeting around 97% in classifying of M3 with other sub-types. Our results are based on real world image data from a Haematology Department.Universiti Sains Islam Malaysia and the Ministry of Higher Education, Malaysi

A New Strategy for the Morphological and Colorimetric Recognition of Erythrocytes for the Diagnosis of Forms of Anemia based on Microscopic Color Images of Blood Smears

The detection of red blood cells based on morphology and colorimetric appearance is very important in improving hematology diagnostics. There are automatons capable of detecting certain forms, but these have limitations with regard to the formal identification of red blood cells because they consider certain cells to be red blood cells when they are not and vice versa. Other automata have limitations in their operation because they do not cover a sufficient area of the blood smear. In spite of their performance, biologists have very often resorted to the manual analysis of blood smears under an optical microscope for a morphological and colorimetric study. In this paper, we present a new strategy for semi-automatic identification of red blood cells based on their isolation, their automatic color segmentation using Otsu's algorithm and their morphology. The algorithms of our method have been implemented in the programming environment of the scientific software MATLAB resulting in an artificial intelligence application. The application, once launched, allows the biologist to select a region of interest containing the erythrocyte to be characterized, then a set of attributes are computed extracted from this target red blood cell. These attributes include compactness, perimeter, area, morphology, white and red proportions of the erythrocyte, etc. The types of anemia treated in this work concern the iron-deficiency, sickle-cell or falciform, thalassemia, hemolytic, etc. forms. The results obtained are excellent because they highlight different forms of anemia contracted in a patient.Comment: ISIS

Automatic quantification of the microvascular density on whole slide images, applied to paediatric brain tumours

Angiogenesis is a key phenomenon for tumour progression, diagnosis and treatment in brain tumours and more generally in oncology. Presently, its precise, direct quantitative assessment can only be done on whole tissue sections immunostained to reveal vascular endothelial cells. But this is a tremendous task for the pathologist and a challenge for the computer since digitised whole tissue sections, whole slide images (WSI), contain typically around ten gigapixels. We define and implement an algorithm that determines automatically, on a WSI at objective magnification $40\times$, the regions of tissue, the regions without blur and the regions of large puddles of red blood cells, and constructs the mask of blur-free, significant tissue on the WSI. Then it calibrates automatically the optical density ratios of the immunostaining of the vessel walls and of the counterstaining, performs a colour deconvolution inside the regions of blur-free tissue, and finds the vessel walls inside these regions by selecting, on the image resulting from the colour deconvolution, zones which satisfy a double-threshold criterion. A mask of vessel wall regions on the WSI is produced. The density of microvessels is finally computed as the fraction of the area of significant tissue which is occupied by vessel walls. We apply this algorithm to a set of 186 WSI of paediatric brain tumours from World Health Organisation grades I to IV. The segmentations are of very good quality although the set of slides is very heterogeneous. The computation time is of the order of a fraction of an hour for each WSI on a modest computer. The computed microvascular density is found to be robust and strongly correlates with the tumour grade. This method requires no training and can easily be applied to other tumour types and other stainings

Fully automated segmentation and tracking of the intima media thickness in ultrasound video sequences of the common carotid artery

Abstract—The robust identification and measurement of the intima media thickness (IMT) has a high clinical relevance because it represents one of the most precise predictors used in the assessment of potential future cardiovascular events. To facilitate the analysis of arterial wall thickening in serial clinical investigations, in this paper we have developed a novel fully automatic algorithm for the segmentation, measurement, and tracking of the intima media complex (IMC) in B-mode ultrasound video sequences. The proposed algorithm entails a two-stage image analysis process that initially addresses the segmentation of the IMC in the first frame of the ultrasound video sequence using a model-based approach; in the second step, a novel customized tracking procedure is applied to robustly detect the IMC in the subsequent frames. For the video tracking procedure, we introduce a spatially coherent algorithm called adaptive normalized correlation that prevents the tracking process from converging to wrong arterial interfaces. This represents the main contribution of this paper and was developed to deal with inconsistencies in the appearance of the IMC over the cardiac cycle. The quantitative evaluation has been carried out on 40 ultrasound video sequences of the common carotid artery (CCA) by comparing the results returned by the developed algorithm with respect to ground truth data that has been manually annotated by clinical experts. The measured IMTmean ± standard deviation recorded by the proposed algorithm is 0.60 mm ± 0.10, with a mean coefficient of variation (CV) of 2.05%, whereas the corresponding result obtained for the manually annotated ground truth data is 0.60 mm ± 0.11 with a mean CV equal to 5.60%. The numerical results reported in this paper indicate that the proposed algorithm is able to correctly segment and track the IMC in ultrasound CCA video sequences, and we were encouraged by the stability of our technique when applied to data captured under different imaging conditions. Future clinical studies will focus on the evaluation of patients that are affected by advanced cardiovascular conditions such as focal thickening and arterial plaques

A Survey on Deep Learning in Medical Image Analysis

Deep learning algorithms, in particular convolutional networks, have rapidly become a methodology of choice for analyzing medical images. This paper reviews the major deep learning concepts pertinent to medical image analysis and summarizes over 300 contributions to the field, most of which appeared in the last year. We survey the use of deep learning for image classification, object detection, segmentation, registration, and other tasks and provide concise overviews of studies per application area. Open challenges and directions for future research are discussed.Comment: Revised survey includes expanded discussion section and reworked introductory section on common deep architectures. Added missed papers from before Feb 1st 201

Automated segmentation of tissue images for computerized IHC analysis

This paper presents two automated methods for the segmentation ofimmunohistochemical tissue images that overcome the limitations of themanual approach aswell as of the existing computerized techniques. The first independent method, based on unsupervised color clustering, recognizes automatically the target cancerous areas in the specimen and disregards the stroma; the second method, based on colors separation and morphological processing, exploits automated segmentation of the nuclear membranes of the cancerous cells. Extensive experimental results on real tissue images demonstrate the accuracy of our techniques compared to manual segmentations; additional experiments show that our techniques are more effective in immunohistochemical images than popular approaches based on supervised learning or active contours. The proposed procedure can be exploited for any applications that require tissues and cells exploration and to perform reliable and standardized measures of the activity of specific proteins involved in multi-factorial genetic pathologie