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: 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: Cardiac dynamics suppression is a main issue for visual improvement and computation of tissue mechanical properties in IntraVascular UltraSound (IVUS). Although in recent times several motion compensation techniques have arisen, there is a lack of objective evaluation of motion reduction in in vivo pullbacks. We consider that the assessment protocol deserves special attention for the sake of a clinical applicability as reliable as possible. Our work focuses on defining a quality measure and a validation protocol assessing IVUS motion compensation. On the grounds of continuum mechanics laws we introduce a novel score measuring motion reduction in in vivo sequences. Synthetic experiments validate the proposed score as measure of motion parameters accuracy; while results in in vivo pullbacks show its reliability in clinical cases.

Abstract: As any iterative technique, it is a necessary condition a stop criterion for terminating Evolutionary Algorithms (EA). In the case of optimization methods, the algorithm should stop at the time it has reached a steady state so it can not improve results anymore. Assessing the reliability of termination conditions for EAs is of prime importance. A wrong or weak stop criterion can negatively aect both the computational eort and the nal result.
In this Thesis, we introduce a statistical framework for assessing whether a termination condition is able to stop EA at its steady state. In one hand a numeric approximation to steady states to detect the point in which EA population has lost its diversity has been presented for EA termination. This approximation has been applied to dierent EA paradigms based on diversity and a selection of functions covering the properties most relevant for EA convergence. Experiments show that our condition works regardless of the search space dimension and function landscape and Dierential Evolution (DE) arises as the best paradigm. On the other hand, we use a regression model in order to determine the requirements ensuring that a measure derived from EA evolving population is related to the distance to the optimum in xspace.
Our theoretical framework is analyzed across several benchmark test functions
and two standard termination criteria based on function improvement in f-space and EA population x-space distribution for the DE paradigm. Results validate our statistical framework as a powerful tool for determining the capability of a measure for terminating EA and select the x-space distribution as the best-suited for accurately stopping DE in real-world applications.