Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Automatic segmentation of neonatal images using convex optimization and coupled level sets

Accurate segmentation of neonatal brain MR images remains challenging mainly due to their poor spatial resolution, inverted contrast between white matter and gray matter, and high intensity inhomogeneity. Most existing methods for neonatal brain segmentation are atlas-based and voxel-wise. Although active contour/surface models with geometric information constraint have been successfully applied to adult brain segmentation, they are not fully explored in the neonatal image segmentation. In this paper, we propose a novel neonatal image segmentation method by combining local intensity information, atlas spatial prior, and cortical thickness constraint in a single level-set framework. Besides, we also provide a robust and reliable tissue surface initialization for the proposed method by using a convex optimization technique. Thus, tissue segmentation, as well as inner and outer cortical surface reconstruction, can be obtained simultaneously. The proposed method has been tested on a large neonatal dataset, and the validation on 10 neonatal brain images (with manual segmentations) shows very promising results

Segmentation of Infant Brain Using Nonnegative Matrix Factorization

This study develops an atlas-based automated framework for segmenting infants\u27 brains from magnetic resonance imaging (MRI). For the accurate segmentation of different structures of an infant\u27s brain at the isointense age (6-12 months), our framework integrates features of diffusion tensor imaging (DTI) (e.g., the fractional anisotropy (FA)). A brain diffusion tensor (DT) image and its region map are considered samples of a Markov-Gibbs random field (MGRF) that jointly models visual appearance, shape, and spatial homogeneity of a goal structure. The visual appearance is modeled with an empirical distribution of the probability of the DTI features, fused by their nonnegative matrix factorization (NMF) and allocation to data clusters. Projecting an initial high-dimensional feature space onto a low-dimensional space of the significant fused features with the NMF allows for better separation of the goal structure and its background. The cluster centers in the latter space are determined at the training stage by the K-means clustering. In order to adapt to large infant brain inhomogeneities and segment the brain images more accurately, appearance descriptors of both the first-order and second-order are taken into account in the fused NMF feature space. Additionally, a second-order MGRF model is used to describe the appearance based on the voxel intensities and their pairwise spatial dependencies. An adaptive shape prior that is spatially variant is constructed from a training set of co-aligned images, forming an atlas database. Moreover, the spatial homogeneity of the shape is described with a spatially uniform 3D MGRF of the second-order for region labels. In vivo experiments on nine infant datasets showed promising results in terms of the accuracy, which was computed using three metrics: the 95-percentile modified Hausdorff distance (MHD), the Dice similarity coefficient (DSC), and the absolute volume difference (AVD). Both the quantitative and visual assessments confirm that integrating the proposed NMF-fused DTI feature and intensity MGRF models of visual appearance, the adaptive shape prior, and the shape homogeneity MGRF model is promising in segmenting the infant brain DTI

Atlas-Free Surface Reconstruction of the Cortical Grey-White Interface in Infants

BACKGROUND: The segmentation of the cortical interface between grey and white matter in magnetic resonance images (MRI) is highly challenging during the first post-natal year. First, the heterogeneous brain maturation creates important intensity fluctuations across regions. Second, the cortical ribbon is highly folded creating complex shapes. Finally, the low tissue contrast and partial volume effects hamper cortex edge detection in parts of the brain. METHODS AND FINDINGS: We present an atlas-free method for segmenting the grey-white matter interface of infant brains in T2-weighted (T2w) images. We used a broad characterization of tissue using features based not only on local contrast but also on geometric properties. Furthermore, inaccuracies in localization were reduced by the convergence of two evolving surfaces located on each side of the inner cortical surface. Our method has been applied to eleven brains of one- to four-month-old infants. Both quantitative validations against manual segmentations and sulcal landmarks demonstrated good performance for infants younger than two months old. Inaccuracies in surface reconstruction increased with age in specific brain regions where the tissue contrast decreased with maturation, such as in the central region. CONCLUSIONS: We presented a new segmentation method which achieved good to very good performance at the grey-white matter interface depending on the infant age. This method should reduce manual intervention and could be applied to pathological brains since it does not require any brain atlas

HyperDense-Net: A hyper-densely connected CNN for multi-modal image segmentation

Recently, dense connections have attracted substantial attention in computer vision because they facilitate gradient flow and implicit deep supervision during training. Particularly, DenseNet, which connects each layer to every other layer in a feed-forward fashion, has shown impressive performances in natural image classification tasks. We propose HyperDenseNet, a 3D fully convolutional neural network that extends the definition of dense connectivity to multi-modal segmentation problems. Each imaging modality has a path, and dense connections occur not only between the pairs of layers within the same path, but also between those across different paths. This contrasts with the existing multi-modal CNN approaches, in which modeling several modalities relies entirely on a single joint layer (or level of abstraction) for fusion, typically either at the input or at the output of the network. Therefore, the proposed network has total freedom to learn more complex combinations between the modalities, within and in-between all the levels of abstraction, which increases significantly the learning representation. We report extensive evaluations over two different and highly competitive multi-modal brain tissue segmentation challenges, iSEG 2017 and MRBrainS 2013, with the former focusing on 6-month infant data and the latter on adult images. HyperDenseNet yielded significant improvements over many state-of-the-art segmentation networks, ranking at the top on both benchmarks. We further provide a comprehensive experimental analysis of features re-use, which confirms the importance of hyper-dense connections in multi-modal representation learning. Our code is publicly available at https://www.github.com/josedolz/HyperDenseNet.Comment: Paper accepted at IEEE TMI in October 2018. Last version of this paper updates the reference to the IEEE TMI paper which compares the submissions to the iSEG 2017 MICCAI Challeng

Contributions of Continuous Max-Flow Theory to Medical Image Processing

Discrete graph cuts and continuous max-flow theory have created a paradigm shift in many areas of medical image processing. As previous methods limited themselves to analytically solvable optimization problems or guaranteed only local optimizability to increasingly complex and non-convex functionals, current methods based now rely on describing an optimization problem in a series of general yet simple functionals with a global, but non-analytic, solution algorithms. This has been increasingly spurred on by the availability of these general-purpose algorithms in an open-source context. Thus, graph-cuts and max-flow have changed every aspect of medical image processing from reconstruction to enhancement to segmentation and registration. To wax philosophical, continuous max-flow theory in particular has the potential to bring a high degree of mathematical elegance to the field, bridging the conceptual gap between the discrete and continuous domains in which we describe different imaging problems, properties and processes. In Chapter 1, we use the notion of infinitely dense and infinitely densely connected graphs to transfer between the discrete and continuous domains, which has a certain sense of mathematical pedantry to it, but the resulting variational energy equations have a sense of elegance and charm. As any application of the principle of duality, the variational equations have an enigmatic side that can only be decoded with time and patience. The goal of this thesis is to show the contributions of max-flow theory through image enhancement and segmentation, increasing incorporation of topological considerations and increasing the role played by user knowledge and interactivity. These methods will be rigorously grounded in calculus of variations, guaranteeing fuzzy optimality and providing multiple solution approaches to addressing each individual problem