Abstract: Empirical and mechanistic models differ in their approaches to the analysis of pharmacological effect. Whereas the parameters of the former are not physical constants those of the latter embody the nature, often complex, of biology. Empirical models are exclusively used for curve fitting, merely to characterize the shape of the E/[A] curves. Mechanistic models, on the contrary, enable the examination of mechanistic hypotheses by parameter simulation. Regretfully, the many parameters that mechanistic models may include can represent a great difficulty for curve fitting, representing, thus, a challenge for computational method development. In the present study some empirical and mechanistic models are shown and the connections, which may appear in a number of cases between them, are analyzed from the curves they yield. It may be concluded that systematic and careful curve shape analysis can be extremely useful for the understanding of receptor function, ligand classification and drug discovery, thus providing a common language for the communication between pharmacologists and medicinal chemists.

Abstract: This paper deals with the recognition of symbols and structural textures in architectural plans using string matching techniques. A plan is represented by an attributed graph whose nodes represent characteristic points and whose edges represent segments. Symbols and textures can be seen as a set of regions, i.e. closed loops in the graph, with a particular arrangement. The search for a symbol involves a graph matching between the regions of a model graph and the regions of the graph representing the document. Discriminating a texture means a clustering of neighbouring regions of this graph. Both procedures involve a similarity measure between graph regions. A string codification is used to represent the sequence of outlining edges of a region. Thus, the similarity between two regions is defined in terms of the string edit distance between their boundary strings. The use of string matching allows the recognition method to work also under presence of distortion.

Abstract: Cardiovascular Diseases, specially those affecting the Left Ventricle (LV), are the leading cause of death in developed countries with approximately a 30% of all global deaths. In order to address this public health concern, physicians focus on diagnosis and therapy planning. On one hand, early and accurate detection of Regional Wall Motion Abnormalities (RWMA) significantly contributes to a quick diagnosis and prevents the patient to reach more severe stages. On the other hand, a thouroughly knowledge of the normal gross anatomy of the LV, as well as, the distribution of its muscular fibers is crucial for designing specific interventions and therapies (such as pacemaker implanction). Statistical models obtained from the analysis of different imaging modalities allow the computation of the normal ranges of variation within a given population. Normality models are a valuable tool for the definition of objective criterions quantifying the degree of (anomalous) deviation of the LV function and anatomy for a given subject. The creation of statistical models involve addressing three main issues: extraction of data from images, definition of a common domain for comparison of data across patients and designing appropriate statistical analysis schemes. In this PhD thesis we present generic image processing tools for the creation of statistical models of the LV anatomy and function. On one hand, we use differential geometry concepts to define a computational framework (the Normalized Parametric Domain, NPD) suitable for the comparison and fusion of several clinical scores obtained over the LV. On the other hand, we present a variational approach (the Harmonic Phase Flow, HPF) for the estimation of myocardial motion that provides dense and continuous vector fields without overestimating motion at injured areas. These tools are used for the creation of statistical models. Regarding anatomy, we obtain an atlas jointly modelling, both, LV gross anatomy and fiber architecture. Regarding function, we compute normality patterns of scores characterizing the (global and local) LV function and explore, for the first time, the configuration of local scores better suited for RWMA detection.

Abstract: Cardiovascular diseases are a leading cause of death in developed countries. Most of them are caused by arterial (specially coronary) diseases, mainly caused by plaque accumulation. Such pathology narrows blood flow (stenosis) and affects artery bio- mechanical elastic properties (atherosclerosis). In the last decades, IntraVascular UltraSound (IVUS) has become a usual imaging technique for the diagnosis and follow up of arterial diseases. IVUS is a catheter-based imaging technique which shows a sequence of cross sections of the artery under study. Inspection of a single image gives information about the percentage of stenosis. Meanwhile, inspection of longitudinal views provides information about artery bio-mechanical properties, which can prevent a fatal outcome of the cardiovascular disease. On one hand, dynamics of arteries (due to heart pumping among others) is a major artifact for exploring tissue bio-mechanical properties. On the other one, manual stenosis measurements require a manual tracing of vessel borders, which is a time-consuming task and might suffer from inter-observer variations. This PhD thesis proposes several image processing tools for exploring vessel dy- namics and structures. We present a physics-based model to extract, analyze and correct vessel in-plane rigid dynamics and to retrieve cardiac phase. Furthermore, we introduce a deterministic-statistical method for automatic vessel borders detection. In particular, we address adventitia layer segmentation. An accurate validation pro- tocol to ensure reliable clinical applicability of the methods is a crucial step in any proposal of an algorithm. In this thesis we take special care in designing a valida- tion protocol for each approach proposed and we contribute to the in vivo dynamics validation with a quantitative and objective score to measure the amount of motion suppressed.