The provision of clean drinking water typically involves treatment processes to remove contaminants. The conventional process involves coagulation with hydrolysing metal salts, typically of aluminium (‘alum’) or trivalent iron (‘ferric’). Along with the product water this also produces a waste by-product, or sludge. The fact of increasing sludge production — due to higher levels of treatment and greater volume of water supply — conflicts with modern demands for environmental best practice, leading to higher financial costs. A further issue is the significant quantity of water that is held up in the sludge, and wasted. / One means of dealing with these problems is to dewater the sludge further. This reduces the volume of waste to be disposed of. The consistency is also improved (e.g. for the purpose of landfilling). And a significant amount of water can be recovered. The efficiency, and efficacy, of this process depends on the dewaterability of the sludge.In fact, good dewaterability is vital to the operation of conventional drinking water treatment plants (WTP’s). The usual process of separating the particulates, formed from a blend of contaminants and coagulated precipitate, relies on ‘clarification’ and ‘thickening’, which are essentially settling operations of solid–liquid separation.WTP operators — and researchers — do attempt to measure sludge dewaterability, but usually rely on empirical characterisation techniques that do not tell the full story and can even mislead. Understanding of the physical and chemical nature of the sludge is also surprisingly rudimentary, considering the long history of these processes. / The present work begins by reviewing the current state of knowledge on raw water and sludge composition, with special focus on solid aluminium and iron phases and on fractal aggregate structure. Next the theory of dewatering is examined, with the adopted phenomenological theory contrasted with empirical techniques and other theories.The foundation for subsequent analyses is laid by experimental work which establishes the solid phase density of WTP sludges. Additionally, alum sludges are found to contain pseudoböhmite, while 2-line ferrihydrite and goethite are identified in ferric sludges. / A key hypothesis is that dewaterability is partly determined by the treatment conditions. To investigate this, numerous WTP sludges were studied that had been generated under diverse conditions: some plant samples were obtained, and the remainder were generated in the laboratory (results were consistent). Dewaterability was characterised for each sludge in concentration ranges relevant to settling, centrifugation and filtration using models developed by LANDMAN and WHITE inter alia; it is expressed in terms of both equilibrium and kinetic parameters, py(φ) and R(φ) respectively.This work confirmed that dewaterability is significantly influenced by treatment conditions.The strongest correlations were observed when varying coagulation pH and coagulant dose. At high doses precipitated coagulant controls the sludge behaviour, and dewaterability is poor. Dewaterability deteriorates as pH is increased for high-dose alum sludges; other sludges are less sensitive to pH. These findings can be linked to the faster coagulation dynamics prevailing at high coagulant and alkali dose.Alum and ferric sludges in general had comparable dewaterabilities, and the characteristics of a magnesium sludge were similar too.Small effects on dewaterability were observed in response to variations in raw water organic content and shearing. Polymer flocculation and conditioning appeared mainly to affect dewaterability at low sludge concentrations. Ageing did not produce clear changes in dewaterability.Dense, compact particles are known to dewater better than ‘fluffy’ aggregates or flocs usually encountered in drinking water treatment. This explains the superior dewaterability of a sludge containing powdered activated carbon (PAC). Even greater improvements were observed following a cycle of sludge freezing and thawing for a wide range of WTP sludges. / Further aspects considered in the present work include deviations from simplifying assumptions that are usually made. Specifically: investigation of long-time dewatering behaviour, wall effects, non-isotropic stresses, and reversibility of dewatering (or ‘elasticity’).Several other results and conclusions, of both theoretical and experimental nature, are presented on topics of subsidiary or peripheral interest that are nonetheless important for establishing a reliable basis for research in this area. / This work has proposed links between industrial drinking water coagulation conditions, sludge dewaterability from settling to filtration, and the microstructure of the aggregates making up that sludge. This information can be used when considering the operation or design of a WTP in order to optimise sludge dewaterability, within the constraints of producing drinking water of acceptable quality.

Whereas manually drawn contours could contain artifacts related to hand tremor, automatically detected contours could contain noise and inaccuracies due to limitations or errors in the procedures for the detection and segmentation of the related regions. To improve the further step of description, modeling procedures are desired to eliminate the artifacts in a given contour, while preserving the important and significant details present in the contour. In this work, are presented a couple of polygonal modeling methods, first a method applied direct on the original contour and other derived from the turning angle function. Both methods use the following parametrization Smin e µmax to infer about removing or maintain a given segment. By the using of the mentioned parameters the proposed methods could be configured according to the application problem. Both methods have been shown eficient to reduce the influence of noise and artifacts while preserving relevant characteristic for further analysis. Systems to support the diagnosis by images (CAD) and retrieval of images by content (CBIR) use shape descriptor methods to make possible to infer about factors existing in a given contour or as base to classify groups with dierent patterns. Shape factors methods should represent a value that is aected by the shape of an object, thus it is possible to characterize the presence of a factor in the contour or identify similarity among contours. Shape factors should be invariant to rotation, translation or scale. In the present work there are proposed the following shape features: index of the presence of convex region (XRTAF ), index of the presence of concave regions (V RTAF ), index of convexity (CXTAF ), two measures of fractal dimension (DFTAF e DF1 TAF ) and the index of spiculation (ISTAF ). All derived from the smoothed turning angle function. The smoothed turning angle function represent the contour in terms of their concave and convex regions. The polygonal modeling and the shape descriptors methods were applied on the breast masses classification issue to evaluate their performance. The polygonal modeling procedure proposed in this work provided higher compression and better polygonal fitness. The best classification accuracies, on discriminating between benign masses and malignant tumors, obtain for XRTAF , V RTAF , CXTAF , DFTAF , DF1 TAF and ISTAF , in terms of area under the receiver operating characteristics curve, were 0:92, 0:92, 0:93, 0:93, 0:92 e 0:94, respectively. / Contornos obtidos manualmente podem conter ruídos e artefatos oriundos de tremores da mão bem como contornos obtidos automaticamente podem os conter dado a problemas na etapa de segmentação. Para melhorar os resultados da etapa de representação e descrição, são necessários métodos capazes de reduzir a influência dos ruídos e artefatos enquanto mantém características relevantes da forma. Métodos de aproximação poligonal têm como objetivo a remoção de ruídos e artefatos presentes nos contornos e a melhor representação da forma com o menor número possível de segmentos de retas. Nesta disserta ção são propostos dois métodos de aproximação poligonal, um aplicado diretamente no contorno e outro que é obtido a partir da função tangencial do contorno original. Ambos os métodos fazem uso dos parâmetros Smin e µmax para inferirem sobre a permanência ou remoção de um dado segmento. Com a utilização destes parâmetros os métodos podem ser configurados para serem utilizados em vários tipos de aplicações. Ambos os métodos mostram-se eficientes na remoção de ruídos e artefatos, enquanto que características relevantes para etapas de pós-processamento são mantidas. Sistemas de apoio ao diagnóstico por imagens e de recuperação de imagens por conte údo fazem uso de métodos descritores de forma para que seja possível inferir sobre características presentes em um dado contorno ou ainda como base para medir a dissimilaridade entre contornos. Métodos descritores de características são capazes de representar um contorno por um número, assim é possível estabelecer a presença de uma característica no contorno ou ainda identificar uma possível similaridade entre os contornos. Métodos para extração de características devem ser invariantes a rotação, translação e escala. Nesta dissertação são propostos os seguintes métodos descritores de características: índice de presença de regiões convexas (XRTAF ), índice da presença de regiões côncavas (V RTAF ), índice de convexidade (CXTAF ), duas medidas de dimensão fractal (DFTAF e DF1 TAF ) e o índice de espículos (ISTAF ). Todos aplicados sobre a função tangencial suavizada. A função tangencial suavizada representa o contorno em termos de suas regiões côncavas e regiões convexas. Os métodos de aproximação poligonal e descritores de características foram aplicados para o problema de classificação de lesões de mama. Os resultados obtidos, mostraram que os métodos de aproximação poligonal propostos neste trabalho resultam em polígonos mais compactos e com melhor representação do contorno original. Os melhores resultados de classificação, na discriminação entre lesões benignas e tumores malignos, obtidos por XRTAF , V RTAF , CXTAF , DFTAF , DF1 TAF e ISTAF , em termos da área sob a curva ROC, foram 0:92, 0:92, 0:93, 0:93, 0:92 e 0:94, respectivamente. / Mestre em Ciência da Computação

Tato diplomová práce se zabývá teorií fraktálů a popisuje patričné potíže při zavedení pojmu fraktál. Dále se v práci navrhuje několik metod, které se použijí na aproximaci fraktálních dimenzí různých množin zobrazených na zařízeních s konečným rozlišením. Tyto metody se otestují na takových množinách, jejichž dimenze známe, a na závěr se výsledky porovnávají.

Existuje mnoho různých způsobů jak analyzovat disperzní systémy a fyzikálně chemické processy ke kterým v takových systémech dochází. Tato práce byla zaměřena na charakterizaci těchto procesů pomocí metod harmonické fraktální analýzy. Obrazová data sledovaných systémů byly analyzovány pomocí waveletové analýzy. V průběhu práce byly navrženy různé optimalizace samotné analýzy, převážně zaměřené na odstranění manuálních operací během analýzy a tyto optimalizace byly také inkorporovány do softérového vybavení pro Harmonickou Fraktální Analýzu HarFA, který je vyvíjen na Fakultě chemické, VUT Brno.

Fractals is a relatively new mathematical topic which received thorough treatment only starting with 1960's. Fractals can be observed everywhere in nature and in day-to-day life. To give a few examples, common fractals are the spiral cactus, the romanesco broccoli, human brain and the outline of the Swedish map. Fractal dimension is a dimension which need not take integer values. In fractal geometry, a fractal dimension is a ratio providing an index of the complexity of fractal pattern with regard to how the local geometry changes with the scale at which it is measured. In recent years, fractal analysis is used increasingly in many areas of engineering and technology. Among others, fractal analysis is used in signal and image compression, computer and video design, neuroscience and fractal based cancer modelling and diagnosing.   This study consists of two main parts. The first part of the study aims to understand the appearance of an irregular Cantor set generated by the chaotic dynamical system generated by the logistic function on the unit interval [0,1]. In order to understand this irregular Cantor set, we studied the topological properties of the Cantor Middle-thirds set and the generalised Cantor sets, all of which have zero length. The necessity to compare these sets with regard to their size led us to the second part of this paper, namely the dimension studies of fractals. More complex fractals were presented in the second part, three definitions of dimension were introduced. The fractal dimension of the irregular Cantor set generated by the logistic mapping was estimated and we found that the Hausdorff dimension has the widest scope and greatest flexibility in the fractal studies. / Fraktaler är ett relativt nytt ämne inom matematik som fick sitt stora genomslag först efter 60-talet.  En fraktal är ett självliknande mönster med struktur i alla skalor. Några vardagliga exempel på fraktaler är spiralkaktus, romanescobroccoli, mänskliga hjärnan, blodkärlen och Sveriges fastlandskust. Bråktalsdimension är en typ av dimension där dimensionsindexet tillåts att anta alla icke-negativa reella tal. Inom fraktalgeometri kan dimensionsindexet betraktas som ett komplexitetsindex av mönstret med avseende på hur den lokala geometrin förändras beroende på vilken skala mönstret betraktas i. Under det senaste decenniet har fraktalanalysen använts alltmer flitigt inom tekniska och vetenskapliga tillämpningar. Bland annat har fraktalanalysen använts i signal- och bildkompression, dator- och videoformgivning, neurovetenskap och fraktalbaserad cancerdiagnos.   Denna studie består av två huvuddelar. Den första delen fokuserar på att förstår hur en fraktal kan uppstå i ett kaotiskt dynamiskt system. För att vara mer specifik studerades den logistiska funktionen och hur denna ickelinjära avbildning genererar en oregelbunden Cantormängd på intervalet [0,1]. Vidare, för att förstå den oregelbundna Cantormängden studerades Cantormängden (eng. the Cantor Middle-Thirds set) och de generaliserade Cantormängderna, vilka alla har noll längd. För att kunna jämföra de olika Cantormängderna med avseende på storlek, leds denna studie vidare till dimensionsanalys av fraktaler som är huvudämnet i den andra delen av denna studie. Olika topologiska fraktaler presenterades, tre olika definitioner av dimension introducerades, bland annat lådräkningsdimensionen och Hausdorffdimensionen. Slutligen approximerades dimensionen av den oregelbundna Cantormängden med hjälp av Hausdorffdimensionen. Denna studie demonstrerar att Hausdorffdimensionen har större omfattning och mer flexibilitet för fraktalstudier.

Das Ziel dieser Arbeit besteht in der Erforschung des Zusammenhangs zwischen der Struktur der Metalloberfläche und der Verbundfestigkeit von thermisch gefügten Thermoplast-Metall-Verbunden. Dazu wird für die Haftungsmechanismen Stoff-, Kraft- und Formschluss an einem Minimalbeispiel rechnerisch gezeigt, dass verschiedene Oberflächenmerkmale (wahre Oberfläche, Strukturdichte, Aspektverhältnis, Hinterschnitte, Substrukturen) mit der Verbundfestigkeit in Verbindung stehen. Basierend darauf werden Oberflächenkenngrößen (standardisierte Rauheitsparameter, fraktale Dimension) gewählt, die die haftungsfördernden Strukturmerkmale möglichst umfassend einbeziehen. Daraus werden Hypothesen abgeleitet, die die Prognostizierbarkeit der Verbundfestigkeit aus Oberflächenkenngrößen für Thermoplast-Metall-Verbunde postulieren. Die experimentelle Überprüfung erfolgt an Aluminium im Verbund mit Polyamid 6 bzw. Polypropylen in Rohrtorsions-, Rohrzug- sowie Zugscherversuchen. Die Einstellung der Oberflächenstruktur des Aluminiums erfolgt durch mechanisches Strahlen, alkalisches Ätzen, thermisches Spritzen sowie Laserstrukturieren. Die Erfassung der Oberflächenstruktur erfolgt taktil sowie aus Querschliffaufnahmen. Die Höhe der Verbundfestigkeit kann anhand der Oberflächenstruktur erklärt und teilweise mit hoher Korrelation quantitativ in Verbindung gebracht werden. Bei taktiler Messung verhindert jedoch eine unzureichende Erfassung bestimmter Strukturmerkmale eine exakte Abbildung der tatsächlichen Oberflächenstruktur. Bei der Erfassung der Oberflächenstruktur aus Querschliffaufnahmen stellt die erreichbare Bildauflösung und -qualität einen limitierenden Faktor dar. Ebenso können aus der Oberflächenstruktur keine individuellen, strukturspezifischen Versagensmechanismen abgeleitet werden.:Inhaltsverzeichnis 5 Abbildungsverzeichnis 9 Tabellenverzeichnis 14 Abkürzungsverzeichnis 16 Symbolverzeichnis 17 1 Motivation 20 2 Stand der Wissenschaft und Technik 22 2.1 Verwendete Begriffe 22 2.2 Verbundwerkstoffe und Werkstoffverbunde 22 2.2.1 Faser-Kunststoff-Verbunde 24 2.2.2 Polymer-Metall-Verbunde 25 2.3 Fügen von Polymer-Metall-Verbunden 27 2.3.1 In-Mold Assembly 28 2.3.2 Kleben 28 2.3.3 Montage 29 2.3.4 Thermisches Fügen 31 2.4 Prüfung der Verbundfestigkeit 34 2.4.1 Prüfkörpergeometrien 34 2.4.2 Beständigkeit gegen Umwelteinflüsse 36 2.5 Verfahren zur Vorbehandlung der Metalloberfläche 38 2.5.1 Mechanisches Strahlen 39 2.5.2 Laserstrukturieren 40 2.5.3 Chemische und elektrochemische Verfahren 43 2.5.4 Beschichten 43 2.5.5 Weitere Verfahren 44 3 Zusammenhang zwischen Oberflächenstruktur und Verbundfestigkeit 46 3.1 Haftungsmechanismen 47 3.1.1 Stoffschluss 48 3.1.2 Kraftschluss 50 3.1.3 Formschluss 51 3.1.4 Skalenabhängigkeit 53 3.1.5 Eigenspannungen 54 3.1.6 Folgerungen 54 3.2 Charakterisierung der Oberflächenstruktur und Korrelation mit der Verbundfestigkeit 55 3.2.1 Standardisierte Rauheitsparameter 56 3.2.2 Fraktale Dimension 58 3.2.3 Anwendungsbeispiel 59 4 Zielstellung 62 4.1 Folgerungen aus dem Stand der Wissenschaft und Technik 62 4.2 Forschungshypothesen 63 5 Experimentelle Vorgehensweise 64 5.1 Charakterisierung der Ausgangswerkstoffe 64 5.2 Vorbehandlung der Metalloberflächen 67 5.2.1 Mechanisches Strahlen und alkalisches Ätzen 67 5.2.2 Thermisches Spritzen 68 5.2.3 Laserstrukturieren 68 5.3 Charakterisierung der Oberflächenstruktur 69 5.4 Mechanische Verbundprüfung 71 5.5 Verwendeter Fügeprozess 73 5.6 Statistische Betrachtung 75 6 Ergebnisse und Diskussion 77 6.1 Verbundfestigkeit in Abhängigkeit von der Oberflächenvorbehandlung 77 6.1.1 Rohrproben 77 6.1.1.1 Oberflächencharakteristika und Benetzung 77 6.1.1.2 Verbundfestigkeit und Korrelation mit Oberflächenkennwerten 81 6.1.1.3 Bruchflächenanalyse 85 6.1.2 Zugscherproben 90 6.1.2.1 Oberflächencharakteristika und Benetzung 90 6.1.2.2 Verbundfestigkeit und Korrelation mit den Oberflächenkennwerten 91 6.1.2.3 Bruchflächenanalyse 93 6.1.3 Ergebnisdiskussion 95 6.2 Verbundfestigkeit in Abhängigkeit von der Skalierung 97 6.2.1 Oberflächencharakteristika und Benetzung 97 6.2.2 Verbundfestigkeit und Korrelation mit Oberflächenkennwerten 102 6.2.3 Bruchflächenanalyse 102 6.2.4 Ergebnissdiskussion 106 7 Zusammenfassung und Folgerungen 108 8 Ausblick 112 Literaturverzeichnis 115 Anhang 129 / The aim of this work is to investigate the relationship between the structure of the metal surface and the compound strength of thermally joined thermoplastic-metal compounds. For this purpose, equations are derived for the adhesion mechanisms of material, force and form closure using a minimal example, which link various surface characteristics (true surface, structure density, aspect ratio, undercuts, substructures) with the compound strength. Based on this, surface parameters (standardized roughness parameters, fractal dimension) are chosen that incorporate the adhesion-promoting structural features as comprehensively as possible. From this, hypotheses are derived that postulate the predictability of compound strength from surface parameters for thermoplastic-metal composites. Experimental verification is carried out on aluminum in compounds with polyamide 6 or polypropylene in hollow cylinder torsion tests, hollow cylinder tensile tests as well as tensile shear tests. The surface of the aluminum is structured by mechanical blasting, alkaline etching, thermal spraying and laser structuring. The surface structure is recorded tactilely and from transverse micrographs. The height of the compound strength can be explained on the basis of surface structure and, in part, quantitatively related with high correlation. However, in the case of tactile measurement, nondetection of certain structural features prevents accurate mapping of the actual surface structure. When recording the surface structure from cross-section images, the achievable image resolution and quality is the limiting factor. Likewise, no individual, structure-specific failure mechanisms can be derived from the surface structure.:Inhaltsverzeichnis 5 Abbildungsverzeichnis 9 Tabellenverzeichnis 14 Abkürzungsverzeichnis 16 Symbolverzeichnis 17 1 Motivation 20 2 Stand der Wissenschaft und Technik 22 2.1 Verwendete Begriffe 22 2.2 Verbundwerkstoffe und Werkstoffverbunde 22 2.2.1 Faser-Kunststoff-Verbunde 24 2.2.2 Polymer-Metall-Verbunde 25 2.3 Fügen von Polymer-Metall-Verbunden 27 2.3.1 In-Mold Assembly 28 2.3.2 Kleben 28 2.3.3 Montage 29 2.3.4 Thermisches Fügen 31 2.4 Prüfung der Verbundfestigkeit 34 2.4.1 Prüfkörpergeometrien 34 2.4.2 Beständigkeit gegen Umwelteinflüsse 36 2.5 Verfahren zur Vorbehandlung der Metalloberfläche 38 2.5.1 Mechanisches Strahlen 39 2.5.2 Laserstrukturieren 40 2.5.3 Chemische und elektrochemische Verfahren 43 2.5.4 Beschichten 43 2.5.5 Weitere Verfahren 44 3 Zusammenhang zwischen Oberflächenstruktur und Verbundfestigkeit 46 3.1 Haftungsmechanismen 47 3.1.1 Stoffschluss 48 3.1.2 Kraftschluss 50 3.1.3 Formschluss 51 3.1.4 Skalenabhängigkeit 53 3.1.5 Eigenspannungen 54 3.1.6 Folgerungen 54 3.2 Charakterisierung der Oberflächenstruktur und Korrelation mit der Verbundfestigkeit 55 3.2.1 Standardisierte Rauheitsparameter 56 3.2.2 Fraktale Dimension 58 3.2.3 Anwendungsbeispiel 59 4 Zielstellung 62 4.1 Folgerungen aus dem Stand der Wissenschaft und Technik 62 4.2 Forschungshypothesen 63 5 Experimentelle Vorgehensweise 64 5.1 Charakterisierung der Ausgangswerkstoffe 64 5.2 Vorbehandlung der Metalloberflächen 67 5.2.1 Mechanisches Strahlen und alkalisches Ätzen 67 5.2.2 Thermisches Spritzen 68 5.2.3 Laserstrukturieren 68 5.3 Charakterisierung der Oberflächenstruktur 69 5.4 Mechanische Verbundprüfung 71 5.5 Verwendeter Fügeprozess 73 5.6 Statistische Betrachtung 75 6 Ergebnisse und Diskussion 77 6.1 Verbundfestigkeit in Abhängigkeit von der Oberflächenvorbehandlung 77 6.1.1 Rohrproben 77 6.1.1.1 Oberflächencharakteristika und Benetzung 77 6.1.1.2 Verbundfestigkeit und Korrelation mit Oberflächenkennwerten 81 6.1.1.3 Bruchflächenanalyse 85 6.1.2 Zugscherproben 90 6.1.2.1 Oberflächencharakteristika und Benetzung 90 6.1.2.2 Verbundfestigkeit und Korrelation mit den Oberflächenkennwerten 91 6.1.2.3 Bruchflächenanalyse 93 6.1.3 Ergebnisdiskussion 95 6.2 Verbundfestigkeit in Abhängigkeit von der Skalierung 97 6.2.1 Oberflächencharakteristika und Benetzung 97 6.2.2 Verbundfestigkeit und Korrelation mit Oberflächenkennwerten 102 6.2.3 Bruchflächenanalyse 102 6.2.4 Ergebnissdiskussion 106 7 Zusammenfassung und Folgerungen 108 8 Ausblick 112 Literaturverzeichnis 115 Anhang 129

<p>Alzheimer’s disease (AD) is a degenerative disease with progressive deterioration of neural networks in the brain. Fractal dimension analysis (FD) of resting state blood oxygen level dependent (BOLD) signals acquired using functional magnetic resonance imaging (fMRI) allows us to quantify complex signalling in the brain and may offer a window into the network erosion. This novel approach can provide a sensitive tool to examine early stages of AD. As AD progresses, we expect to see a reduction in brain connectivity and signal complexity concurrent with biochemical changes (e.g. altered levels of N-acetyl aspartate (NAA), myoinositol (mI) and glutamate as measured using magnetic resonance spectroscopy, MRS), volumetric changes and abnormally high levels of brain iron.</p> <p>Over a series of 4 studies we examined the relationship of BOLD signal complexity and functional connectivity with documented MRI markers of pathology in AD (n=38) as compared to normal controls (NC) (n=16). AD subjects were in early stage of illness (mild to moderate impairment on the mini mental state exam, MMSE). We validated the temporal (short term (within minutes) and longer term (over a number of months)) consistency of FD measurement and choice of BOLD acquisition method (spiral vs. EPI), provided MRI sequence repeat time (TR) was kept constant. FD reduction (decrease in signal complexity) correlated with worsening pathological values on MRS (­NAA decrease and mI increase) and with a decrease in functional connectivity. This demonstrates that FD (signal complexity) reduces in proportion to AD severity. FD reduction is connected to functional connectivity measured through resting state network (RSN) analysis suggesting the reduction in FD relates to neuronal loss rather than altered vascularity. The narrow range of cognitive impairment (such as scores on the MMSE or the clinical dementia rating scale, CDR) likely precluded correlation between these measures and FD or RSN. Functional connectivity (RSN) was also reduced when brain iron levels were increased within certain network nodes (posterior cingulate cortex and lateral parietal cortex). Therefore iron deposition may play a role in network disruption of AD brains.</p> <p>The overall conclusion of this thesis is that signal complexity of BOLD fMRI signals, as measured with FD, may detect early pathology in the progression of AD. FD can detect neuronal changes in deep brain structures before volume loss in these structures and before significant changes in MRS markers were detectable between the AD and NC groups. An FD change mirrors disruptions in functional connectivity but detection is not limited to RSN nodes in the brain. This novel approach could further our understanding of AD and may be applied to other pathologies of the brain.</p> / Doctor of Philosophy (PhD)

En los ultimos años el número de casos de ceguera se ha reducido significativamente. A pesar de este hecho, la Organización Mundial de la Salud estima que un 80% de los casos de pérdida de visión (285 millones en 2010) pueden ser evitados si se diagnostican en sus estadios más tempranos y son tratados de forma efectiva. Para cumplir esta propuesta se pretende que los servicios de atención primaria incluyan un seguimiento oftalmológico de sus pacientes así como fomentar campañas de cribado en centros proclives a reunir personas de alto riesgo. Sin embargo, estas soluciones exigen una alta carga de trabajo de personal experto entrenado en el análisis de los patrones anómalos propios de cada enfermedad. Por lo tanto, el desarrollo de algoritmos para la creación de sistemas de cribado automáticos juga un papel vital en este campo. La presente tesis persigue la identificacion automática del daño retiniano provocado por dos de las patologías más comunes en la sociedad actual: la retinopatía diabética (RD) y la degenaración macular asociada a la edad (DMAE). Concretamente, el objetivo final de este trabajo es el desarrollo de métodos novedosos basados en la extracción de características de la imagen de fondo de ojo y clasificación para discernir entre tejido sano y patológico. Además, en este documento se proponen algoritmos de pre-procesado con el objetivo de normalizar la alta variabilidad existente en las bases de datos publicas de imagen de fondo de ojo y eliminar la contribución de ciertas estructuras retinianas que afectan negativamente en la detección del daño retiniano. A diferencia de la mayoría de los trabajos existentes en el estado del arte sobre detección de patologías en imagen de fondo de ojo, los métodos propuestos a lo largo de este manuscrito evitan la necesidad de segmentación de las lesiones o la generación de un mapa de candidatos antes de la fase de clasificación. En este trabajo, Local binary patterns, perfiles granulométricos y la dimensión fractal se aplican de manera local para extraer información de textura, morfología y tortuosidad de la imagen de fondo de ojo. Posteriormente, esta información se combina de diversos modos formando vectores de características con los que se entrenan avanzados métodos de clasificación formulados para discriminar de manera óptima entre exudados, microaneurismas, hemorragias y tejido sano. Mediante diversos experimentos, se valida la habilidad del sistema propuesto para identificar los signos más comunes de la RD y DMAE. Para ello se emplean bases de datos públicas con un alto grado de variabilidad sin exlcuir ninguna imagen. Además, la presente tesis también cubre aspectos básicos del paradigma de deep learning. Concretamente, se presenta un novedoso método basado en redes neuronales convolucionales (CNNs). La técnica de transferencia de conocimiento se aplica mediante el fine-tuning de las arquitecturas de CNNs más importantes en el estado del arte. La detección y localización de exudados mediante redes neuronales se lleva a cabo en los dos últimos experimentos de esta tesis doctoral. Cabe destacar que los resultados obtenidos mediante la extracción de características "manual" y posterior clasificación se comparan de forma objetiva con las predicciones obtenidas por el mejor modelo basado en CNNs. Los prometedores resultados obtenidos en esta tesis y el bajo coste y portabilidad de las cámaras de adquisión de imagen de retina podrían facilitar la incorporación de los algoritmos desarrollados en este trabajo en un sistema de cribado automático que ayude a los especialistas en la detección de patrones anomálos característicos de las dos enfermedades bajo estudio: RD y DMAE. / In last years, the number of blindness cases has been significantly reduced. Despite this promising news, the World Health Organisation estimates that 80% of visual impairment (285 million cases in 2010) could be avoided if diagnosed and treated early. To accomplish this purpose, eye care services need to be established in primary health and screening campaigns should be a common task in centres with people at risk. However, these solutions entail a high workload for trained experts in the analysis of the anomalous patterns of each eye disease. Therefore, the development of algorithms for automatic screening system plays a vital role in this field. This thesis focuses on the automatic identification of the retinal damage provoked by two of the most common pathologies in the current society: diabetic retinopathy (DR) and age-related macular degeneration (AMD). Specifically, the final goal of this work is to develop novel methods, based on fundus image description and classification, to characterise the healthy and abnormal tissue in the retina background. In addition, pre-processing algorithms are proposed with the aim of normalising the high variability of fundus images and removing the contribution of some retinal structures that could hinder in the retinal damage detection. In contrast to the most of the state-of-the-art works in damage detection using fundus images, the methods proposed throughout this manuscript avoid the necessity of lesion segmentation or the candidate map generation before the classification stage. Local binary patterns, granulometric profiles and fractal dimension are locally computed to extract texture, morphological and roughness information from retinal images. Different combinations of this information feed advanced classification algorithms formulated to optimally discriminate exudates, microaneurysms, haemorrhages and healthy tissues. Through several experiments, the ability of the proposed system to identify DR and AMD signs is validated using different public databases with a large degree of variability and without image exclusion. Moreover, this thesis covers the basics of the deep learning paradigm. In particular, a novel approach based on convolutional neural networks is explored. The transfer learning technique is applied to fine-tune the most important state-of-the-art CNN architectures. Exudate detection and localisation tasks using neural networks are carried out in the last two experiments of this thesis. An objective comparison between the hand-crafted feature extraction and classification process and the prediction models based on CNNs is established. The promising results of this PhD thesis and the affordable cost and portability of retinal cameras could facilitate the further incorporation of the developed algorithms in a computer-aided diagnosis (CAD) system to help specialists in the accurate detection of anomalous patterns characteristic of the two diseases under study: DR and AMD. / En els últims anys el nombre de casos de ceguera s'ha reduït significativament. A pesar d'este fet, l'Organització Mundial de la Salut estima que un 80% dels casos de pèrdua de visió (285 milions en 2010) poden ser evitats si es diagnostiquen en els seus estadis més primerencs i són tractats de forma efectiva. Per a complir esta proposta es pretén que els servicis d'atenció primària incloguen un seguiment oftalmològic dels seus pacients així com fomentar campanyes de garbellament en centres regentats per persones d'alt risc. No obstant això, estes solucions exigixen una alta càrrega de treball de personal expert entrenat en l'anàlisi dels patrons anòmals propis de cada malaltia. Per tant, el desenrotllament d'algoritmes per a la creació de sistemes de garbellament automàtics juga un paper vital en este camp. La present tesi perseguix la identificació automàtica del dany retiniano provocat per dos de les patologies més comunes en la societat actual: la retinopatia diabètica (RD) i la degenaración macular associada a l'edat (DMAE) . Concretament, l'objectiu final d'este treball és el desenrotllament de mètodes novedodos basats en l'extracció de característiques de la imatge de fons d'ull i classificació per a discernir entre teixit sa i patològic. A més, en este document es proposen algoritmes de pre- processat amb l'objectiu de normalitzar l'alta variabilitat existent en les bases de dades publiques d'imatge de fons d'ull i eliminar la contribució de certes estructures retinianas que afecten negativament en la detecció del dany retiniano. A diferència de la majoria dels treballs existents en l'estat de l'art sobre detecció de patologies en imatge de fons d'ull, els mètodes proposats al llarg d'este manuscrit eviten la necessitat de segmentació de les lesions o la generació d'un mapa de candidats abans de la fase de classificació. En este treball, Local binary patterns, perfils granulometrics i la dimensió fractal s'apliquen de manera local per a extraure informació de textura, morfologia i tortuositat de la imatge de fons d'ull. Posteriorment, esta informació es combina de diversos modes formant vectors de característiques amb els que s'entrenen avançats mètodes de classificació formulats per a discriminar de manera òptima entre exsudats, microaneurismes, hemorràgies i teixit sa. Per mitjà de diversos experiments, es valida l'habilitat del sistema proposat per a identificar els signes més comuns de la RD i DMAE. Per a això s'empren bases de dades públiques amb un alt grau de variabilitat sense exlcuir cap imatge. A més, la present tesi també cobrix aspectes bàsics del paradigma de deep learning. Concretament, es presenta un nou mètode basat en xarxes neuronals convolucionales (CNNs) . La tècnica de transferencia de coneixement s'aplica per mitjà del fine-tuning de les arquitectures de CNNs més importants en l'estat de l'art. La detecció i localització d'exudats per mitjà de xarxes neuronals es du a terme en els dos últims experiments d'esta tesi doctoral. Cal destacar que els resultats obtinguts per mitjà de l'extracció de característiques "manual" i posterior classificació es comparen de forma objectiva amb les prediccions obtingudes pel millor model basat en CNNs. Els prometedors resultats obtinguts en esta tesi i el baix cost i portabilitat de les cambres d'adquisión d'imatge de retina podrien facilitar la incorporació dels algoritmes desenrotllats en este treball en un sistema de garbellament automàtic que ajude als especialistes en la detecció de patrons anomálos característics de les dos malalties baix estudi: RD i DMAE. / Colomer Granero, A. (2018). Fundus image analysis for automatic screening of ophthalmic pathologies [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/99745

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