Geometry Processing of Conventionally Produced Mouse Brain Slice Images

Brain mapping research in most neuroanatomical laboratories relies on conventional processing techniques, which often introduce histological artifacts such as tissue tears and tissue loss. In this paper we present techniques and algorithms for automatic registration and 3D reconstruction of conventionally produced mouse brain slices in a standardized atlas space. This is achieved first by constructing a virtual 3D mouse brain model from annotated slices of Allen Reference Atlas (ARA). Virtual re-slicing of the reconstructed model generates ARA-based slice images corresponding to the microscopic images of histological brain sections. These image pairs are aligned using a geometric approach through contour images. Histological artifacts in the microscopic images are detected and removed using Constrained Delaunay Triangulation before performing global alignment. Finally, non-linear registration is performed by solving Laplace's equation with Dirichlet boundary conditions. Our methods provide significant improvements over previously reported registration techniques for the tested slices in 3D space, especially on slices with significant histological artifacts. Further, as an application we count the number of neurons in various anatomical regions using a dataset of 51 microscopic slices from a single mouse brain. This work represents a significant contribution to this subfield of neuroscience as it provides tools to neuroanatomist for analyzing and processing histological data.Comment: 14 pages, 11 figure

Bayesian Spatial Binary Regression for Label Fusion in Structural Neuroimaging

Many analyses of neuroimaging data involve studying one or more regions of interest (ROIs) in a brain image. In order to do so, each ROI must first be identified. Since every brain is unique, the location, size, and shape of each ROI varies across subjects. Thus, each ROI in a brain image must either be manually identified or (semi-) automatically delineated, a task referred to as segmentation. Automatic segmentation often involves mapping a previously manually segmented image to a new brain image and propagating the labels to obtain an estimate of where each ROI is located in the new image. A more recent approach to this problem is to propagate labels from multiple manually segmented atlases and combine the results using a process known as label fusion. To date, most label fusion algorithms either employ voting procedures or impose prior structure and subsequently find the maximum a posteriori estimator (i.e., the posterior mode) through optimization. We propose using a fully Bayesian spatial regression model for label fusion that facilitates direct incorporation of covariate information while making accessible the entire posterior distribution. We discuss the implementation of our model via Markov chain Monte Carlo and illustrate the procedure through both simulation and application to segmentation of the hippocampus, an anatomical structure known to be associated with Alzheimer's disease.Comment: 24 pages, 10 figure

Explainable Anatomical Shape Analysis through Deep Hierarchical Generative Models

Quantification of anatomical shape changes currently relies on scalar global indexes which are largely insensitive to regional or asymmetric modifications. Accurate assessment of pathology-driven anatomical remodeling is a crucial step for the diagnosis and treatment of many conditions. Deep learning approaches have recently achieved wide success in the analysis of medical images, but they lack interpretability in the feature extraction and decision processes. In this work, we propose a new interpretable deep learning model for shape analysis. In particular, we exploit deep generative networks to model a population of anatomical segmentations through a hierarchy of conditional latent variables. At the highest level of this hierarchy, a two-dimensional latent space is simultaneously optimised to discriminate distinct clinical conditions, enabling the direct visualisation of the classification space. Moreover, the anatomical variability encoded by this discriminative latent space can be visualised in the segmentation space thanks to the generative properties of the model, making the classification task transparent. This approach yielded high accuracy in the categorisation of healthy and remodelled left ventricles when tested on unseen segmentations from our own multi-centre dataset as well as in an external validation set, and on hippocampi from healthy controls and patients with Alzheimer's disease when tested on ADNI data. More importantly, it enabled the visualisation in three-dimensions of both global and regional anatomical features which better discriminate between the conditions under exam. The proposed approach scales effectively to large populations, facilitating high-throughput analysis of normal anatomy and pathology in large-scale studies of volumetric imaging

Characterising population variability in brain structure through models of whole-brain structural connectivity

Models of whole-brain connectivity are valuable for understanding neurological function. This thesis seeks to develop an optimal framework for extracting models of whole-brain connectivity from clinically acquired diffusion data. We propose new approaches for studying these models. The aim is to develop techniques which can take models of brain connectivity and use them to identify biomarkers or phenotypes of disease. The models of connectivity are extracted using a standard probabilistic tractography algorithm, modified to assess the structural integrity of tracts, through estimates of white matter anisotropy. Connections are traced between 77 regions of interest, automatically extracted by label propagation from multiple brain atlases followed by classifier fusion. The estimates of tissue integrity for each tract are input as indices in 77x77 ”connectivity” matrices, extracted for large populations of clinical data. These are compared in subsequent studies. To date, most whole-brain connectivity studies have characterised population differences using graph theory techniques. However these can be limited in their ability to pinpoint the locations of differences in the underlying neural anatomy. Therefore, this thesis proposes new techniques. These include a spectral clustering approach for comparing population differences in the clustering properties of weighted brain networks. In addition, machine learning approaches are suggested for the first time. These are particularly advantageous as they allow classification of subjects and extraction of features which best represent the differences between groups. One limitation of the proposed approach is that errors propagate from segmentation and registration steps prior to tractography. This can cumulate in the assignment of false positive connections, where the contribution of these factors may vary across populations, causing the appearance of population differences where there are none. The final contribution of this thesis is therefore to develop a common co-ordinate space approach. This combines probabilistic models of voxel-wise diffusion for each subject into a single probabilistic model of diffusion for the population. This allows tractography to be performed only once, ensuring that there is one model of connectivity. Cross-subject differences can then be identified by mapping individual subjects’ anisotropy data to this model. The approach is used to compare populations separated by age and gender

Template-Cut: A Pattern-Based Segmentation Paradigm

We present a scale-invariant, template-based segmentation paradigm that sets up a graph and performs a graph cut to separate an object from the background. Typically graph-based schemes distribute the nodes of the graph uniformly and equidistantly on the image, and use a regularizer to bias the cut towards a particular shape. The strategy of uniform and equidistant nodes does not allow the cut to prefer more complex structures, especially when areas of the object are indistinguishable from the background. We propose a solution by introducing the concept of a "template shape" of the target object in which the nodes are sampled non-uniformly and non-equidistantly on the image. We evaluate it on 2D-images where the object's textures and backgrounds are similar, and large areas of the object have the same gray level appearance as the background. We also evaluate it in 3D on 60 brain tumor datasets for neurosurgical planning purposes.Comment: 8 pages, 6 figures, 3 tables, 6 equations, 51 reference