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: Optical Flow (OF) is the input of a wide range of decision support systems such as car driver assistance, UAV guiding or medical diagnose. In these real situations, the absence of ground truth forces to assess OF quality using quantities computed from either sequences or the computed optical flow itself. These quantities are generally known as Confidence Measures, CM. Even if we have a proper confidence measure we still need a way to evaluate its ability to discard pixels with an OF prone to have a large error. Current approaches only provide a descriptive evaluation of the CM performance but such approaches are not capable to fairly compare different confidence measures and optical flow algorithms. Thus, it is of prime importance to define a framework and a general road map for the evaluation of optical flow performance.
This thesis provides a framework able to decide which pairs “ optical flow – confidence measure” (OF-CM) are best suited for optical flow error bounding given a confidence level determined by a decision support system. To design this framework we cover the following points:
Descriptive scores. As a first step, we summarize and analyze the sources of inaccuracies in the output of optical flow algorithms. Second, we present several descriptive plots that visually assess CM capabilities for OF error bounding. In addition to the descriptive plots, given a plot representing OF-CM capabilities to bound the error, we provide a numeric score that categorizes the plot according to its decreasing profile, that is, a score assessing CM performance.
Statistical framework. We provide a comparison framework that assesses the best suited OF-CM pair for error bounding that uses a two stage cascade process. First of all we assess the predictive value of the confidence measures by means of a descriptive plot. Then, for a sample of descriptive plots computed over training frames, we obtain a generic curve that will be used for sequences with no ground truth. As a second step, we evaluate the obtained general curve and its capabilities to really reflect the predictive value of a confidence measure using the variability across train frames by means of ANOVA.
The presented framework has shown its potential in the application on clinical decision support systems. In particular, we have analyzed the impact of the different image artifacts such as noise and decay to the output of optical flow in a cardiac diagnose system and we have improved the navigation inside the bronchial tree on bronchoscopy.

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.

Abstract: Lung cancer is one of the most diagnosed cancers among men and women. Actually,
lung cancer accounts for 13% of the total cases with a 5-year global survival
rate in patients. Although Early detection increases survival rate from 38% to 67%, accurate diagnosis remains a challenge. Pathological confirmation requires extracting a sample of the lesion tissue for its biopsy. The preferred procedure for tissue biopsy is called bronchoscopy. A bronchoscopy is an endoscopic technique for the internal exploration of airways which facilitates the performance of minimal invasive interventions with low risk for the patient. Recent advances in bronchoscopic devices have increased their use for minimal invasive diagnostic and intervention procedures, like lung cancer biopsy sampling. Despite the improvement in bronchoscopic device quality, there is a lack of intelligent computational systems for supporting in-vivo clinical decision during examinations. Existing technologies fail to accurately reach the lesion due to several aspects at intervention off-line planning and poor intra-operative guidance at exploration time. Existing guiding systems radiate patients and clinical staff,might be expensive and achieve a suboptimlal 70% of yield boost. Diagnostic yield could be improved reducing radiation and costs by developing intra-operative support systems able to guide the bronchoscopist to the lesion during the intervention. The goal of this PhD thesis is to develop an image-based navigation systemfor intra-operative guidance of bronchoscopists to a target lesion across a path previously planned on a CT-scan. We propose a 3D navigation system which uses the anatomy of video bronchoscopy frames to locate the bronchoscope within the airways. Once the bronchoscope is located, our navigation system is able to indicate the bifurcation which needs to be followed to reach the lesion. In order to facilitate an off-line validation
as realistic as possible, we also present a method for augmenting simulated virtual bronchoscopies with the appearance of intra-operative videos. Experiments performed on augmented and intra-operative videos, prove that our algorithm can be speeded up for an on-line implementation in the operating room.