Abstract: The operational model of agonism assumes that the maximum effect a particular receptor system can achieve (the Em parameter) is fixed. Em estimates are above but close to the asymptotic maximum effects of endogenous agonists. The concept of Em is contradicted by superagonists and those positive allosteric modulators that significantly increase the maximum effect of endogenous agonists. An extension of the operational model is proposed that assumes that the Em parameter does not necessarily have a single value for a receptor system but has multiple values associated to multiple active receptor conformations. The model provides a mechanistic link between active receptor conformation and agonist efficacy, which can be useful for the analysis of agonist response under different receptor scenarios.

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: The framework of this thesis is to study in detail different techniques and tools for medical image registration in order to ease the daily life of clinical experts in cardiology. The first aim of this thesis is providing computer tools for
fusing IVUS and angiogram data is of high clinical interest to help the physicians locate in IVUS data and decide which lesion is observed, how long it is, how far from a bifurcation or another lesions stays, etc. This thesis proves and
validates that we can segment the catheter path in angiographies using geodesic snakes (based on fast marching algorithm), a three-dimensional reconstruction of the catheter inspired in stereo vision and a new technique to fuse IVUS
and angiograms that establishes exact correspondences between them. We have developed a new workstation called iFusion that has four strong advantages: registration of IVUS and angiographic images with sub-pixel precision, it works on- and off-line, it is independent on the X-ray system and there is no need of daily calibration. The second aim of the thesis is devoted to developing a computer-aided analysis of IVUS for image-guided intervention. We have designed, implemented
and validated a robust algorithm for stent extraction and reconstruction from IVUS videos. We consider a very special and recent kind of stents, bioabsorbable stents that represent a great clinical challenge due to their property to be
absorbed by time and thus avoiding the “danger” of neostenosis as one of the main problems of metallic stents. We present a new and very promising algorithm based on an optimized cascade of multiple classifiers to automatically detect individual stent struts of a very novel bioabsorbable drug eluting coronary stent. This problem represents a very challenging target given the variability in contrast, shape and grey levels of the regions to be detected, what is
denoted by the high variability between the specialists (inter-observer variability of 0.14~$\pm$0.12). The obtained results of the automatic strut detection are within the inter-observer variability.

Abstract: Bioabsorbable drug-eluting coronary stents present a very promising improvement to the common metallic ones solving some of the most important problems of stent implantation: the late restenosis. These stents made of poly-L-lactic acid cause a very subtle acoustic shadow (compared to the metallic ones) making difficult the automatic detection and measurements in images. In this paper, we propose a novel approach based on a cascade of GentleBoost classifiers to detect the stent struts using structural features to code the information of the different subregions of the struts. A stochastic gradient descent method is applied to optimize the overall performance of the detector. Validation results of struts detection are very encouraging with an average F-measure of 81%.