Abstract: Chromosome territoriality is not random along the cell cycle and it is mainly governed by intrinsic chromosome factors and gene expression patterns. Conversely, very few studies have explored the factors that determine chromosome territoriality and its influencing factors during meiosis. In this study, we analysed chromosome positioning in murine spermatogenic cells using three-dimensionally fluorescence in situ hybridization-based methodology, which allows the analysis of the entire karyotype. The main objective of the study was to decipher chromosome positioning in a radial axis (all analysed germ-cell nuclei) and longitudinal axis (only spermatozoa) and to identify the chromosomal factors that regulate such an arrangement. Results demonstrated that the radial positioning of chromosomes during spermatogenesis was cell-type specific and influenced by chromosomal factors associated to gene activity. Chromosomes with specific features that enhance transcription (high GC content, high gene density and high numbers of predicted expressed genes) were preferentially observed in the inner part of the nucleus in virtually all cell types. Moreover, the position of the sex chromosomes was influenced by their transcriptional status, from the periphery of the nucleus when its activity was repressed (pachytene) to a more internal position when it is partially activated (spermatid). At pachytene, chromosome positioning was also influenced by chromosome size due to the bouquet formation. Longitudinal chromosome positioning in the sperm nucleus was not random either, suggesting the importance of ordered longitudinal positioning for the release and activation of the paternal genome after fertilisation.

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 vessel displacement is a main artifact in IVUS sequences. It hinders visualization of the main structures in an appropriate orientation and alignment and affects extracting vessel measurements. In this paper, we present a novel approach for image sequence alignment based on spectral analysis, which removes rigid dynamics, preserving at the same time the vessel geometry. First, we suppress the translation by taking, for each frame, the center of mass of the image as origin of coordinates. In polar coordinates with such point as origin, the rotation appears as a horizontal displacement. The translation induces a phase shift in the Fourier coefficients of two consecutive polar images. We estimate the phase by adjusting a regression plane to the phases of the principal frequencies. Experiments show that the presented strategy suppress cardiac motion regardless of the acquisition device. 1.

Abstract: Cardiac Magnetic Resonance images offer the opportunity to study the heart in detail. One of the main issues in its modelling is to create an accurate 3-D reconstruction of the left ventricle from 2-D views. A first step to achieve this goal is the correct registration among the different image planes due to patient movements. In this article, we present an accurate method to correct displacement artifacts using the Normalized Mutual Information. Here, the image views are treated as planes in order to diminish the approximation error caused by the association of a certain thickness, and moved simultaneously to avoid any kind of bias in the alignment process. This method has been validated using real and syntectic plane displacements, yielding promising results.

Abstract: Cardiac diseases are diagnosed and treated through a study of the morphology and dynamics of cardiac arteries. In- travascular Ultrasound (IVUS) imaging is of high interest to physicians since it provides both information. At the current state-of-the-art in image segmentation, a robust detection of the arterial lumen in IVUS demands manual intervention or ECG-gating. Manual intervention is a tedious and time consuming task that requires experienced observers, meanwhile ECG-gating is an acquisition technique not available in all clinical centers. We introduce a parametric algorithm that detects the arterial luminal border in in vivo sequences. The method consist in smoothing the sequences’ level surfaces under a regularized mean curvature flow that admits non-trivial steady states. The flow is based on a measure of the surface local smoothness that takes into account regularity of the surface curvature.