Automatic segmentation and shape analysis of human hippocampus in Alzheimer's disease

The aim of this thesis is to investigate the shape change in hippocampus due to the atrophy in Alzheimer’s disease (AD). To this end, specific algorithms and methodologies were developed to segment the hippocampus from structural magnetic resonance (MR) images and model variations in its shape. We use a multi-atlas based segmentation propagation approach for the segmentation of hippocampus which has been shown to obtain accurate parcellation of brain structures. We developed a supervised method to build a population specific atlas database, by propagating the parcellations from a smaller generic atlas database. Well segmented images are inspected and added to the set of atlases, such that the segmentation capability of the atlas set may be enhanced. The population specific atlases are evaluated in terms of the agreement among the propagated labels when segmenting new cases. Compared with using generic atlases, the population specific atlases obtain a higher agreement when dealing with images from the target population. Atlas selection is used to improve segmentation accuracy. In addition to the conventional selection by image similarity ranking, atlas selection based on maximum marginal relevance (MMR) re-ranking and least angle regression (LAR) sequence are developed for atlas selection. By taking the redundancy among atlases into consideration, diversity criteria are shown to be more efficient in atlas selection which is applicable in the situation where the number of atlases to be fused is limited by the computational resources. Given the segmented hippocampal volumes, statistical shape models (SSMs) of hippocampi are built on the samples to model the shape variation among the population. The correspondence across the training samples of hippocampi is established by a groupwise optimization of the parameterized shape surfaces. The spherical parameterization of the hippocampal surfaces are flatten to facilitate the reparameterization and interpolation. The reparameterization is regularized by viscous fluid, which is solved by a fast implementation based on discrete sine transform. In order to use the hippocampal SSM to describe the shape of an unseen hippocampal surface, we developed a shape parameter estimator based on the expectationmaximization iterative closest points (EM-ICP) algorithm. A symmetric data term is included to achieve the inverse consistency of the transformation between the model and the shape, which gives more accurate reconstruction of the shape from the model. The shape prior modeled by the SSM is used in the maximum a posteriori estimation of the shape parameters, which is shown to enforce the smoothness and avoid the effect of over-fitting. In the study of the hippocampus in AD, we use the SSM to model the hippocampal shape change between the healthy control subjects and patients diagnosed with AD. We identify the regions affected by the atrophy in AD by assessing the spatial difference between the control and AD groups at each corresponding landmark. Localized shape analysis is performed on the regions exhibiting significant inter-group difference, which is shown to improve the discrimination ability of the principal component analysis (PCA) based SSM. The principal components describing the localized shape variability among the population are also shown to display stronger correlation with the decline of episodic memory scores linked to the pathology of hippocampus in AD.