Analysing the Surface Morphology of Colorectal Polyps:Differential Geometry and Pit Pattern Prediction

We present an initial study analysing the surface morphology of colorectal polyps from optical projection tomography. The differential geometry of polyp surfaces, seg-mented using a level sets method, is explored in terms of local, multi-scale shape index and curvedness descriptors. A surface region of interest can be represented using his-tograms of these descriptors. An experiment is described investigating the ability to predict pit pattern categories from these histograms using support vector machines.

Integrated Structural And Functional Biomarkers For Neurodegeneration

Alzheimer\u27s Disease consists of a complex cascade of pathological processes, leading to the death of cortical neurons and development of dementia. Because it is impossible to regenerate neurons that have already died, a thorough understanding of the earlier stages of the disease, before significant neuronal death has occurred, is critical for developing disease-modifying therapies. The various components of Alzheimer\u27s Disease pathophysiology necessitate a variety of measurement techniques. Image-based measurements known as biomarkers can be used to assess cortical thinning and cerebral blood flow, but non-imaging characteristics such as performance on cognitive tests and age are also important determinants of risk of Alzheimer\u27s Disease. Incorporating the various imaging and non-imaging sources of information into a scientifically interpretable and statistically sound model is challenging. In this thesis, I present a method to include imaging data in standard regression analyses in a data-driven and anatomically interpretable manner. I also introduce a technique for disentangling the effect of cortical structure from blood flow, enabling a clearer picture of the signal carried by cerebral blood flow beyond the confounding effects of anatomical structure. In addition to these technical developments in multi-modal image analysis, I show the results of two clinically-oriented studies focusing on the relative importance of various biomarkers for predicting presence of Alzheimer\u27s Disease pathology in the earliest stages of disease. In the first, I present evidence that white matter hyperintensities, a marker of small vessel disease, are more highly associated with Alzheimer\u27s Disease pathology than current mainstream imaging biomarkers in elderly control patients. In the second, I show that once Alzheimer\u27s Disease has progressed to the point of noticeable cognitive decline, cognitive tests are as predictive of presence of Alzheimer\u27s pathology as standard imaging biomarkers. Taken together, these studies demonstrate that the relative importance of biomarkers and imaging modalities changes over the course of disease progression, and sophisticated data-driven methods for combining a variety of modalities is likely to lead to greater biological insight into the disease process than a single modality

Morphogenetic Principles of Brain Organisation in Health and Disease

Non-invasive neuroimaging methods, such as MRI, provide a window into the structure of the mammalian brain. However, despite the ubiquity of these methods, the biological interpretation of the information obtained using these tools remains elusive. In order to accurately link this macroscale data to microscale measurements, it is critical that the construct validity is high. This thesis provides novel analyses, pipelines and methods to: i) generate and validate maps of brain organisation obtained via MRI, and ii) demonstrate the utility of these methods in capturing elements of cognition and psychopathology. First, in Chapter 1, I review some of the neuroscientific context for the new methods presented, from cytoarchitecture to gene expression to connectomes. Chapters 2-4 introduce a new method, “Morphometric Similarity Mapping”, which captures the brain organisation of an individual by mapping the relationships of multiple features of the cerebral cortex. Chapter 2 focuses on the development of the analysis pipeline and the graph theoretical features of the resulting morphometric similarity networks (MSNs), with an emphasis on reproducibility. Chapter 3 highlights the generalisability of MSNs to the macaque monkey, linking MSNs to ex vivo tract tracing experiments and presenting new tools for processing non-human imaging data; as well as evidence that MSN topography is organised by cytoarchitectonic features. Chapter 4 is focused on determining the transcriptomic correlates of MSNs using publicly available gene expression maps, and on applying MSNs to examine the relationship between brain organisation and intelligence. Chapter 5 is dedicated to rigorous evaluation of the applicability of MSNs to measure specific disease-relevant phenotypes in 8 rare genetic disorder cohorts. This includes the validation of novel methods for utilising data from both single-cell sequencing technologies and differential gene expression experiments (in multiple tissue types) in analysing neuroimaging and bulk transcriptomic brain maps. Chapter 6 provides a brief summary and presents some ongoing and future projects expanding on this original work. It also importantly discusses a general framework of comparing brain maps, including MSNs and gene expression, as well as other canonical maps of brain structure and function. Altogether, this thesis presents and evaluates novel methods and applications for integrating multimodal neuroimaging data with genetic data derived from multiple tissue types and through various acquisition strategies. It also includes tools for performing these analyses in non-human primates, and pipelines for statistically comparing brain maps. These results not only provide insight into the manifestation of brain-related changes due to various components of human variation, but also provides a framework for evaluating this variation at multiple biological scales purely from non-invasive neuroimaging data

Upper airways segmentation using principal curvatures

Esta tesis propone una nueva técnica para segmentar las vías aéreas superiores. Esta propuesta permite la extracción de estructuras curvilíneas usando curvaturas principales. La propuesta permite la extracción de éstas estructuras en imágenes 2D y 3D. Entre las principales novedades se encuentra la propuesta de un nuevo criterio de parada en la propagación del algoritmo de realce de contraste (operador multi-escala de tipo sombrero alto). De la misma forma, el criterio de parada propuesto es usado para detener los algoritmos de difusión anisotrópica. Además, un nuevo criterio es propuesto para seleccionar las curvaturas principales que conforman las estructuras curvilíneas, que se basa en los criterios propuestos por Steger, Deng et. al. y Armande et. al. Además, se propone un nuevo algoritmo para realizar la supresión de nomáximos que permite reducir la presencia de discontinuidades en el borde de las estructuras curvilíneas. Para extraer los bordes de las estructuras curvilíneas, se utiliza un algoritmo de enlace que incluye un nuevo criterio de distancia para reducir la aparición de agujeros en la estructura final. Finalmente, con base en los resultados obtenidos, se utiliza un algoritmo morfológico para cerrar los agujeros y se aplica un algoritmo de crecimiento de regiones para obtener la segmentación final de las vías respiratorias superiores.This dissertation proposes a new approach to segment the upper airways. This proposal allows the extraction of curvilinear structures based on the principal curvatures. The proposal allows extracting these structures from 2D and 3D images. Among the main novelties is the proposal of a new stopping criterion to stop the propagation of the contrast enhancement algorithm (multiscale top-hat morphological operator). In the same way, the proposed stopping criterion is used to stop the anisotropic diffusion algorithms. In addition, a new criterion is proposed to select the principal curvatures that make up the curvilinear structures, which is based on the criteria proposed by Steger, Deng et. al. and Armande et. al. Furthermore, a new algorithm to perform the non-maximum suppression that allows reducing the presence of discontinuities in the border of curvilinear structures is proposed. To extract the edges of the curvilinear structures, a linking algorithm is used that includes a new distance criterion to reduce the appearance of gaps in the final structure. Finally, based on the obtained results, a morphological algorithm is used to close the gaps and a region growing algorithm to obtain the final upper airways segmentation is applied.Doctor en IngenieríaDoctorad