A normative spatiotemporal MRI atlas of the fetal brain for automatic segmentation and analysis of early brain growth.

Longitudinal characterization of early brain growth in-utero has been limited by a number of challenges in fetal imaging, the rapid change in size, shape and volume of the developing brain, and the consequent lack of suitable algorithms for fetal brain image analysis. There is a need for an improved digital brain atlas of the spatiotemporal maturation of the fetal brain extending over the key developmental periods. We have developed an algorithm for construction of an unbiased four-dimensional atlas of the developing fetal brain by integrating symmetric diffeomorphic deformable registration in space with kernel regression in age. We applied this new algorithm to construct a spatiotemporal atlas from MRI of 81 normal fetuses scanned between 19 and 39 weeks of gestation and labeled the structures of the developing brain. We evaluated the use of this atlas and additional individual fetal brain MRI atlases for completely automatic multi-atlas segmentation of fetal brain MRI. The atlas is available online as a reference for anatomy and for registration and segmentation, to aid in connectivity analysis, and for groupwise and longitudinal analysis of early brain growth

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

Segmentation of brain MRI during early childhood

The objective of this thesis is the development of automatic methods to measure the changes in volume and growth of brain structures in prematurely born infants. Automatic tools for accurate tissue quantification from magnetic resonance images can provide means for understanding how the neurodevelopmental effects of the premature birth, such as cognitive, neurological or behavioural impairment, are related to underlying changes in brain anatomy. Understanding these changes forms a basis for development of suitable treatments to improve the outcomes of premature birth. In this thesis we focus on the segmentation of brain structures from magnetic resonance images during early childhood. Most of the current brain segmentation techniques have been focused on the segmentation of adult or neonatal brains. As a result of rapid development, the brain anatomy during early childhood differs from anatomy of both adult and neonatal brains and therefore requires adaptations of available techniques to produce good results. To address the issue of anatomical differences of the brain during early childhood compared to other age-groups, population-specific deformable and probabilistic atlases are introduced. A method for generation of population-specific prior information in form of a probabilistic atlas is proposed and used to enhance existing segmentation algorithms. The evaluation of registration-based and intensity-based approaches shows the techniques to be complementary in the quality of automatic segmentation in different parts of the brain. We propose a novel robust segmentation method combining the advantages of both approaches. The method is based on multiple label propagation using B-spline non-rigid registration followed by EM segmentation. Intensity inhomogeneity is a shading artefact resulting from the acquisition process, which significantly affects modern high resolution MR data acquired at higher magnetic field strengths. A novel template based method focused on correcting the intensity inhomogeneity in data acquired at higher magnetic field strengths is therefore proposed. The proposed segmentation method combined with proposed intensity inhomogeneity correction method offers a robust tool for quantification of volumes and growth of brain structures during early childhood. The tool have been applied to 67 T1-weigted images of subject at one and two years of age

Quantification of cortical folding using MR image data

The cerebral cortex is a thin layer of tissue lining the brain where neural circuits perform important high level functions including sensory perception, motor control and language processing. In the third trimester the fetal cortex folds rapidly from a smooth sheet into a highly convoluted arrangement of gyri and sulci. Premature birth is a high risk factor for poor neurodevelopmental outcome and has been associated with abnormal cortical development, however the nature of the disruption to developmental processes is not fully understood. Recent developments in magnetic resonance imaging have allowed the acquisition of high quality brain images of preterms and also fetuses in-utero. The aim of this thesis is to develop techniques which quantify folding from these images in order to better understand cortical development in these two populations. A framework is presented that quantifies global and regional folding using curvature-based measures. This methodology was applied to fetuses over a wide gestational age range (21.7 to 38.9 weeks) for a large number of subjects (N = 80) extending our understanding of how the cortex folds through this critical developmental period. The changing relationship between the folding measures and gestational age was modelled with a Gompertz function which allowed an accurate prediction of physiological age. A spectral-based method is outlined for constructing a spatio-temporal surface atlas (a sequence of mean cortical surface meshes for weekly intervals). A key advantage of this method is the ability to do group-wise atlasing without bias to the anatomy of an initial reference subject. Mean surface templates were constructed for both fetuses and preterms allowing a preliminary comparison of mean cortical shape over the postmenstrual age range 28-36 weeks. Displacement patterns were revealed which intensified with increasing prematurity, however more work is needed to evaluate the reliability of these findings.Open Acces

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

The development and application of structural priors for diffuse optical imaging in infants from newborn to two years of age

This thesis describes the development and application of age-appropriate structural priors to improve the localisation accuracy of diffuse optical tomography (DOT) approaches in infants aged from birth to two years of age. Knowledge of the target cranial anatomy, known as a structural prior, is required to produce three-dimensional images localising concentration changes to the cortex. A structural prior would ideally be subject-specific, i.e. derived from structural magnetic resonance imaging (MRI) data from each specific subject. Requiring a structural scan from every infant participant, however, is not feasible and undermines many of the benefits of DOT. A review was conducted to catalogue available infant structural MRI data, and selected data was then used to produce structural priors for infants aged 1- to 24-months. Conventional analyses using functional near-infrared spectroscopy (fNIRS) implicitly assume that head size and array position are constant across infants. Using DOT, the validity of assuming these parameters constant in a longitudinal infant cohort was investigated. The results show that this assumption is reasonable at the group-level in infants aged 5- to 12-months but becomes less valid for smaller group sizes. A DOT approach was determined to illicit more subtle effects of activation, particularly for smaller group sizes and expected responses. Using state-of-the-art MRI data from the Developing Human Connectome Project, a database of structural priors of the neonatal head was produced for infants aged pre-term to term-equivalent age. A leave-one-out approach was used to determine how best to find a match between a given infant and a model from the database, and how best to spatially register the model to minimise the anatomical and localisation errors relative to subject-specific anatomy. Model selection based on the 10/20 scalp positions was determined to be the best method (of those based on external features of the head) to minimise these errors

The INCF Digital Atlasing Program: Report on Digital Atlasing Standards in the Rodent Brain

The goal of the INCF Digital Atlasing Program is to provide the vision and direction necessary to make the rapidly growing collection of multidimensional data of the rodent brain (images, gene expression, etc.) widely accessible and usable to the international research community. This Digital Brain Atlasing Standards Task Force was formed in May 2008 to investigate the state of rodent brain digital atlasing, and formulate standards, guidelines, and policy recommendations.

Our first objective has been the preparation of a detailed document that includes the vision and specific description of an infrastructure, systems and methods capable of serving the scientific goals of the community, as well as practical issues for achieving
the goals. This report builds on the 1st INCF Workshop on Mouse and Rat Brain Digital Atlasing Systems (Boline et al., 2007, _Nature Preceedings_, doi:10.1038/npre.2007.1046.1) and includes a more detailed analysis of both the current state and desired state of digital atlasing along with specific recommendations for achieving these goals

Neonatal brain image segmentation in longitudinal MRI studies

In study of early brain development, tissue segmentation of neonatal brain MR images remains challenging because of the insufficient image quality due to the properties of developing tissues.. Among various brain tissue segmentation algorithms, atlas-based brain image segmentation can potentially achieve good segmentation results on neonatal brain images. However, their performances rely on both the quality of the atlas and the spatial correspondence between the atlas and the to-be-segmented image. Moreover, it is difficult to build a population atlas for neonates due to the requirement of a large set of tissue-segmented neonatal brain images. To combat these obstacles, we present a longitudinal neonatal brain image segmentation framework by taking advantage of the longitudinal data acquired at late time-point to build a subject-specific tissue probabilistic atlas. Specifically, tissue segmentation of the neonatal brain is formulated as two iterative steps of bias correction and probabilistic-atlas-based tissue segmentation, along with the longitudinal atlas reconstructed by the late time image of the same subject. The proposed method has been evaluated qualitatively through visual inspection and quantitatively by comparing with manual delineations and two population-atlas-based segmentation methods. Experimental results show that the utilization of a subject-specific probabilistic atlas can substantially improve tissue segmentation of neonatal brain images