Monitoring mesenchymal stem cell cultures using image processing and pattern recognition techniques

Stem cells have attracted tremendous interest in recent times due to their promise in providing innovative new treatments for a great range of currently debilitating diseases. This is due to their potential ability to regenerate and repair damaged tissue, and hence restore lost body function, in a manner beyond the body's usual healing process. Bone marrow-derived mesenchymal stem cells or bone marrow stromal cells are one type of adult stem cells that are of particular interest. Since they are derived from a living human adult donor, they do not have the ethical issues associated with the use of human embryonic stem cells. They are also able to be taken from a patient or other donors with relative ease and then grown readily in the laboratory for clinical application. Despite the attractive properties of bone marrow stromal cells, there is presently no quick and easy way to determine the quality of a sample of such cells. Presently, a sample must be grown for weeks and subject to various time-consuming assays, under the direction of an expert cell biologist, to determine whether it will be useful. Hence there is a great need for innovative new ways to assess the quality of cell cultures for research and potential clinical application. The research presented in this thesis investigates the use of computerised image processing and pattern recognition techniques to provide a quicker and simpler method for the quality assessment of bone marrow stromal cell cultures. In particular, aim of this work is to find out whether it is possible, through the use of image processing and pattern recognition techniques, to predict the growth potential of a culture of human bone marrow stromal cells at early stages, before it is readily apparent to a human observer. With the above aim in mind, a computerised system was developed to classify the quality of bone marrow stromal cell cultures based on phase contrast microscopy images. Our system was trained and tested on mixed images of both healthy and unhealthy bone marrow stromal cell samples taken from three different patients. This system, when presented with 44 previously unseen bone marrow stromal cell culture images, outperformed human experts in the ability to correctly classify healthy and unhealthy cultures. The system correctly classified the health status of an image 88% of the time compared to an average of 72% of the time for human experts. Extensive training and testing of the system on a set of 139 normal sized images and 567 smaller image tiles showed an average performance of 86% and 85% correct classifications, respectively. The contributions of this thesis include demonstrating the applicability and potential of computerised image processing and pattern recognition techniques to the task of quality assessment of bone marrow stromal cell cultures. As part of this system, an image normalisation method has been suggested and a new segmentation algorithm has been developed for locating cell regions of irregularly shaped cells in phase contrast images. Importantly, we have validated the efficacy of both the normalisation and segmentation method, by demonstrating that both methods quantitatively improve the classification performance of subsequent pattern recognition algorithms, in discriminating between cell cultures of differing health status. We have shown that the quality of a cell culture of bone marrow stromal cells may be assessed without the need to either segment individual cells or to use time-lapse imaging. Finally, we have proposed a set of features, that when extracted from the cell regions of segmented input images, can be used to train current state of the art pattern recognition systems to predict the quality of bone marrow stromal cell cultures earlier and more consistently than human experts.

A Pattern Recognition Model of Voice-Based Personal Verification Systems for Forensic Applications

Abstract-The success of automatic speaker recognition in laboratory environments suggests applications in forensic science for establishing the Identity of individuals on the basis of features extracted from speech. A theoretical model for such a verification scheme for continuous normaliy distributed featureIss developed. The three cases of using a) single feature, b)multipliendependent measurements of a single feature, and c)multpleindependent features are explored.The number iofndependent features needed for areliable personal identification is computed based on the theoretcal model and an expklatory study of some speech featues.

Automatic physical activity pattern recognition and meal intake modelling in type 1 diabetes for their inclusion in artificial pancreas systems

La diabetes comprende un conjunto de enfermedades metabólicas que se caracterizan por concentraciones de glucosa en sangre anormalmente altas. En el caso de la diabetes tipo 1 (T1D, por sus siglas en inglés), esta situación es debida a una ausencia total de secreción endógena de insulina, lo que impide a la mayoría de tejidos usar la glucosa. En tales circunstancias, se hace necesario el suministro exógeno de insulina para preservar la vida del paciente; no obstante, siempre con la precaución de evitar caídas agudas de la glucemia por debajo de los niveles recomendados de seguridad. Además de la administración de insulina, las ingestas y la actividad física son factores fundamentales que influyen en la homeostasis de la glucosa. En consecuencia, una gestión apropiada de la T1D debería incorporar estos dos fenómenos fisiológicos, en base a una identificación y un modelado apropiado de los mismos y de sus sorrespondientes efectos en el balance glucosa-insulina. En particular, los sistemas de páncreas artificial –ideados para llevar a cabo un control automático de los niveles de glucemia del paciente– podrían beneficiarse de la integración de esta clase de información. La primera parte de esta tesis doctoral cubre la caracterización del efecto agudo de la actividad física en los perfiles de glucosa. Con este objetivo se ha llevado a cabo una revisión sistemática de la literatura y meta-análisis que determinen las respuestas ante varias modalidades de ejercicio para pacientes con T1D, abordando esta caracterización mediante unas magnitudes que cuantifican las tasas de cambio en la glucemia a lo largo del tiempo. Por otro lado, una identificación fiable de los periodos con actividad física es un requisito imprescindible para poder proveer de esa información a los sistemas de páncreas artificial en condiciones libres y ambulatorias. Por esta razón, la segunda parte de esta tesis está enfocada a la propuesta y evaluación de un sistema automático diseñado para reconocer periodos de actividad física, clasificando su nivel de intensidad (ligera, moderada o vigorosa); así como, en el caso de periodos vigorosos, identificando también la modalidad de ejercicio (aeróbica, mixta o de fuerza). En este sentido, ambos aspectos tienen una influencia específica en el mecanismo metabólico que suministra la energía para llevar a cabo el ejercicio y, por tanto, en las respuestas glucémicas en T1D. En este trabajo se aplican varias combinaciones de técnicas de aprendizaje máquina y reconocimiento de patrones sobre la fusión multimodal de señales de acelerometría y ritmo cardíaco, las cuales describen tanto aspectos mecánicos del movimiento como la respuesta fisiológica del sistema cardiovascular ante el ejercicio. Después del reconocimiento de patrones se incorpora también un módulo de filtrado temporal para sacar partido a la considerable coherencia temporal presente en los datos, una redundancia que se origina en el hecho de que en la práctica, las tendencias en cuanto a actividad física suelen mantenerse estables a lo largo de cierto tiempo, sin fluctuaciones rápidas y repetitivas. El tercer bloque de esta tesis doctoral aborda el tema de las ingestas en el ámbito de la T1D. En concreto, se propone una serie de modelos compartimentales y se evalúan éstos en función de su capacidad para describir matemáticamente el efecto remoto de las concetraciones plasmáticas de insulina exógena sobre las tasas de eleiminación de la glucosa atribuible a la ingesta; un aspecto hasta ahora no incorporado en los principales modelos de paciente para T1D existentes en la literatura. Los datos aquí utilizados se obtuvieron gracias a un experimento realizado por el Institute of Metabolic Science (Universidad de Cambridge, Reino Unido) con 16 pacientes jóvenes. En el experimento, de tipo ‘clamp’ con objetivo variable, se replicaron los perfiles individuales de glucosa, según lo observado durante una visita preliminar tras la ingesta de una cena con o bien alta carga glucémica, o bien baja. Los seis modelos mecanísticos evaluados constaban de: a) submodelos de doble compartimento para las masas de trazadores de glucosa, b) un submodelo de único compartimento para reflejar el efecto remoto de la insulina, c) dos tipos de activación de este mismo efecto remoto (bien lineal, bien con un punto de corte), y d) diversas condiciones iniciales. ABSTRACT Diabetes encompasses a series of metabolic diseases characterized by abnormally high blood glucose concentrations. In the case of type 1 diabetes (T1D), this situation is caused by a total absence of endogenous insulin secretion, which impedes the use of glucose by most tissues. In these circumstances, exogenous insulin supplies are necessary to maintain patient’s life; although caution is always needed to avoid acute decays in glycaemia below safe levels. In addition to insulin administrations, meal intakes and physical activity are fundamental factors influencing glucose homoeostasis. Consequently, a successful management of T1D should incorporate these two physiological phenomena, based on an appropriate identification and modelling of these events and their corresponding effect on the glucose-insulin balance. In particular, artificial pancreas systems –designed to perform an automated control of patient’s glycaemia levels– may benefit from the integration of this type of information. The first part of this PhD thesis covers the characterization of the acute effect of physical activity on glucose profiles. With this aim, a systematic review of literature and metaanalyses are conduced to determine responses to various exercise modalities in patients with T1D, assessed via rates-of-change magnitudes to quantify temporal variations in glycaemia. On the other hand, a reliable identification of physical activity periods is an essential prerequisite to feed artificial pancreas systems with information concerning exercise in ambulatory, free-living conditions. For this reason, the second part of this thesis focuses on the proposal and evaluation of an automatic system devised to recognize physical activity, classifying its intensity level (light, moderate or vigorous) and for vigorous periods, identifying also its exercise modality (aerobic, mixed or resistance); since both aspects have a distinctive influence on the predominant metabolic pathway involved in fuelling exercise, and therefore, in the glycaemic responses in T1D. Various combinations of machine learning and pattern recognition techniques are applied on the fusion of multi-modal signal sources, namely: accelerometry and heart rate measurements, which describe both mechanical aspects of movement and the physiological response of the cardiovascular system to exercise. An additional temporal filtering module is incorporated after recognition in order to exploit the considerable temporal coherence (i.e. redundancy) present in data, which stems from the fact that in practice, physical activity trends are often maintained stable along time, instead of fluctuating rapid and repeatedly. The third block of this PhD thesis addresses meal intakes in the context of T1D. In particular, a number of compartmental models are proposed and compared in terms of their ability to describe mathematically the remote effect of exogenous plasma insulin concentrations on the disposal rates of meal-attributable glucose, an aspect which had not yet been incorporated to the prevailing T1D patient models in literature. Data were acquired in an experiment conduced at the Institute of Metabolic Science (University of Cambridge, UK) on 16 young patients. A variable-target glucose clamp replicated their individual glucose profiles, observed during a preliminary visit after ingesting either a high glycaemic-load or a low glycaemic-load evening meal. The six mechanistic models under evaluation here comprised: a) two-compartmental submodels for glucose tracer masses, b) a single-compartmental submodel for insulin’s remote effect, c) two types of activations for this remote effect (either linear or with a ‘cut-off’ point), and d) diverse forms of initial conditions.

Pattern recognition using invariants defined from higher order spectra : 2-D image inputs

A new algorithm for extracting features from images for object recognition is described. The algorithm uses higher order spectra to provide desirable invariance properties, to provide noise immunity, and to incorporate nonlinearity into the feature extraction procedure thereby allowing the use of simple classifiers. An image can be reduced to a set of 1D functions via the Radon transform, or alternatively, the Fourier transform of each 1D projection can be obtained from a radial slice of the 2D Fourier transform of the image according to the Fourier slice theorem. A triple product of Fourier coefficients, referred to as the deterministic bispectrum, is computed for each 1D function and is integrated along radial lines in bifrequency space. Phases of the integrated bispectra are shown to be translation- and scale-invariant. Rotation invariance is achieved by a regrouping of these invariants at a constant radius followed by a second stage of invariant extraction. Rotation invariance is thus converted to translation invariance in the second step. Results using synthetic and actual images show that isolated, compact clusters are formed in feature space. These clusters are linearly separable, indicating that the nonlinearity required in the mapping from the input space to the classification space is incorporated well into the feature extraction stage. The use of higher order spectra results in good noise immunity, as verified with synthetic and real images. Classification of images using the higher order spectra-based algorithm compares favorably to classification using the method of moment invariants

Pattern recognition using invariants defined from higher order spectra - one-dimensional inputs

A new approach to pattern recognition using invariant parameters based on higher order spectra is presented. In particular, invariant parameters derived from the bispectrum are used to classify one-dimensional shapes. The bispectrum, which is translation invariant, is integrated along straight lines passing through the origin in bifrequency space. The phase of the integrated bispectrum is shown to be scale and amplification invariant, as well. A minimal set of these invariants is selected as the feature vector for pattern classification, and a minimum distance classifier using a statistical distance measure is used to classify test patterns. The classification technique is shown to distinguish two similar, but different bolts given their one-dimensional profiles. Pattern recognition using higher order spectral invariants is fast, suited for parallel implementation, and has high immunity to additive Gaussian noise. Simulation results show very high classification accuracy, even for low signal-to-noise ratios.

A Fuzzy Approximation Scheme for Sequential Learning in Pattern Recognition

An adaptive learning scheme, based on a fuzzy approximation to the gradient descent method for training a pattern classifier using unlabeled samples, is described. The objective function defined for the fuzzy ISODATA clustering procedure is used as the loss function for computing the gradient. Learning is based on simultaneous fuzzy decisionmaking and estimation. It uses conditional fuzzy measures on unlabeled samples. An exponential membership function is assumed for each class, and the parameters constituting these membership functions are estimated, using the gradient, in a recursive fashion. The induced possibility of occurrence of each class is useful for estimation and is computed using 1) the membership of the new sample in that class and 2) the previously computed average possibility of occurrence of the same class. An inductive entropy measure is defined in terms of induced possibility distribution to measure the extent of learning. The method is illustrated with relevant examples.

Pattern Recognition With Weighted Complex Networks

In this paper we introduce a weighted complex networks model to investigate and recognize structures of patterns. The regular treating in pattern recognition models is to describe each pattern as a high-dimensional vector which however is insufficient to express the structural information. Thus, a number of methods are developed to extract the structural information, such as different feature extraction algorithms used in pre-processing steps, or the local receptive fields in convolutional networks. In our model, each pattern is attributed to a weighted complex network, whose topology represents the structure of that pattern. Based upon the training samples, we get several prototypal complex networks which could stand for the general structural characteristics of patterns in different categories. We use these prototypal networks to recognize the unknown patterns. It is an attempt to use complex networks in pattern recognition, and our result shows the potential for real-world pattern recognition. A spatial parameter is introduced to get the optimal recognition accuracy, and it remains constant insensitive to the amount of training samples. We have discussed the interesting properties of the prototypal networks. An approximate linear relation is found between the strength and color of vertexes, in which we could compare the structural difference between each category. We have visualized these prototypal networks to show that their topology indeed represents the common characteristics of patterns. We have also shown that the asymmetric strength distribution in these prototypal networks brings high robustness for recognition. Our study may cast a light on understanding the mechanism of the biologic neuronal systems in object recognition as well.

Skeleton based visual pattern recognition. Applications to tabletop interaction

211 p. :il.

Computer Vision and Pattern Recognition Technologies for Construction

This book will be of particular interest to academics, researchers, and graduate students at universities and industrial practitioners seeking to apply mobile and pervasive computing systems to improve construction industry productivity.

SEARCH FOR THE BASIC REGULARITIES OF THE TRANSITION EMISSION OF EUROPIUM(II) ION IN COMPLEX FLUORIDES USING PATTERN-RECOGNITION

The relationship between structures of complex fluorides and spectral structure of Eu(II) ion in complex fluorides (AB(m)F(n)) is investigated by means of pattern recognition methods, such as KNN, ALKNN, BAYES, LLM, SIMCA and PCA. A learning set consisting of 32 f-f transition emission host compounds and 31 d-f transition emission host compounds and a test set consisting of 27 host compounds were characterized by 12 crystal structural parameters. These parameters, i.e. features, were reduced from 12 to 6 by multiple criteria for the classification of these host compounds as f-f transition emission or d-f transition emission. A recognition rate from 79.4 to 96.8% and prediction capabilities from 85.2 to 92.6% were obtained. According to the above results, the spectral structures of Eu(II) ion in seven unknown host lattices were predicted.

Integrating Symbolic and Neural Processing in a Self-Organizing Architechture for Pattern Recognition and Prediction

British Petroleum (89A-1204); Defense Advanced Research Projects Agency (N00014-92-J-4015); National Science Foundation (IRI-90-00530); Office of Naval Research (N00014-91-J-4100); Air Force Office of Scientific Research (F49620-92-J-0225)

An Active Pattern Recognition Architecture for Mobile Robots

An active, attentionally-modulated recognition architecture is proposed for object recognition and scene analysis. The proposed architecture forms part of navigation and trajectory planning modules for mobile robots. Key characteristics of the system include movement planning and execution based on environmental factors and internal goal definitions. Real-time implementation of the system is based on space-variant representation of the visual field, as well as an optimal visual processing scheme utilizing separate and parallel channels for the extraction of boundaries and stimulus qualities. A spatial and temporal grouping module (VWM) allows for scene scanning, multi-object segmentation, and featural/object priming. VWM is used to modulate a tn~ectory formation module capable of redirecting the focus of spatial attention. Finally, an object recognition module based on adaptive resonance theory is interfaced through VWM to the visual processing module. The system is capable of using information from different modalities to disambiguate sensory input.

Learning Temporal Contexts and Priming-Preparation Modes for Pattern Recognition

The system presented here is based on neurophysiological and electrophysiological data. It computes three types of increasingly integrated temporal and probability contexts, in a bottom-up mode. To each of these contexts corresponds an increasingly specific top-down priming effect on lower processing stages, mostly pattern recognition and discrimination. Contextual learning of time intervals, events' temporal order or sequential dependencies and events' prior probability results from the delivery of large stimuli sequences. This learning gives rise to emergent properties which closely match the experimental data.