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

Cerebral atrophy in mild cognitive impairment and Alzheimer disease: rates and acceleration.

OBJECTIVE: To quantify the regional and global cerebral atrophy rates and assess acceleration rates in healthy controls, subjects with mild cognitive impairment (MCI), and subjects with mild Alzheimer disease (AD). METHODS: Using 0-, 6-, 12-, 18-, 24-, and 36-month MRI scans of controls and subjects with MCI and AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we calculated volume change of whole brain, hippocampus, and ventricles between all pairs of scans using the boundary shift integral. RESULTS: We found no evidence of acceleration in whole-brain atrophy rates in any group. There was evidence that hippocampal atrophy rates in MCI subjects accelerate by 0.22%/year2 on average (p = 0.037). There was evidence of acceleration in rates of ventricular enlargement in subjects with MCI (p = 0.001) and AD (p < 0.001), with rates estimated to increase by 0.27 mL/year2 (95% confidence interval 0.12, 0.43) and 0.88 mL/year2 (95% confidence interval 0.47, 1.29), respectively. A post hoc analysis suggested that the acceleration of hippocampal loss in MCI subjects was mainly driven by the MCI subjects that were observed to progress to clinical AD within 3 years of baseline, with this group showing hippocampal atrophy rate acceleration of 0.50%/year2 (p = 0.003). CONCLUSIONS: The small acceleration rates suggest a long period of transition to the pathologic losses seen in clinical AD. The acceleration in hippocampal atrophy rates in MCI subjects in the ADNI seems to be driven by those MCI subjects who concurrently progressed to a clinical diagnosis of AD

Development of a tool for automatic segmentation of the cerebellum in MR images of children

The human cerebellar cortex is a highly foliated structure that supports both motor and complex cognitive functions in humans. Magnetic Resonance Imaging (MRI) is commonly used to explore structural alterations in patients with psychiatric and neurological diseases. The ability to detect regional structural differences in cerebellar lobules may provide valuable insights into disease biology, progression and response to treatment, but has been hampered by the lack of appropriate tools for performing automated structural cerebellar segmentation and morphometry. In this thesis, time intensive manual tracings by an expert neuroanatomist of 16 cerebellar regions on high-resolution T1-weighted MR images of 18 children aged 9-13 years were used to generate the Cape Town Pediatric Cerebellar Atlas (CAPCA18) in the age-appropriate National Institute of Health Pediatric Database (NIHPD) asymmetric template space. An automated pipeline was developed to process the MR images and generate lobule-wise segmentations, as well as a measure of the uncertainty of the label assignments. Validation in an independent group of children with ages similar to those of the children used in the construction of the atlas, yielded spatial overlaps with manual segmentations greater than 70% in all lobules, except lobules VIIb and X. Average spatial overlap of the whole cerebellar cortex was 86%, compared to 78% using the alternative Spatially Unbiased Infra-tentorial Template (SUIT), which was developed using adult images

Unbiased diffeomorphic atlas construction for computational anatomy

pre-printConstruction of population atlases is a key issue in medical image analysis, and particularly in brain mapping. Large sets of images are mapped into a common coordinate system to study intra-population variability and inter-population differences, to provide voxel-wise mapping of functional sites, and help tissue and object segmentation via registration of anatomical labels. Common techniques often include the choice of a template image, which inherently introduces a bias. This paper describes a new method for unbiased construction of atlases in the large deformation diffeomorphic setting. A child neuroimaging autism study serves as a driving application. There is lack of normative data that explains average brain shape and variability at this early stage of development. We present work in progress toward constructing an unbiased MRI atlas of two year of children and the building of a probabilistic atlas of anatomical structures, here the caudate nucleus. Further, we demonstrate the segmentation of new subjects via atlas mapping. Validation of the methodology is performed by comparing the deformed probabilistic atlas with existing manual segmentations

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

ABCD Neurocognitive Prediction Challenge 2019: Predicting individual fluid intelligence scores from structural MRI using probabilistic segmentation and kernel ridge regression

We applied several regression and deep learning methods to predict fluid intelligence scores from T1-weighted MRI scans as part of the ABCD Neurocognitive Prediction Challenge (ABCD-NP-Challenge) 2019. We used voxel intensities and probabilistic tissue-type labels derived from these as features to train the models. The best predictive performance (lowest mean-squared error) came from Kernel Ridge Regression (KRR; $\lambda=10$), which produced a mean-squared error of 69.7204 on the validation set and 92.1298 on the test set. This placed our group in the fifth position on the validation leader board and first place on the final (test) leader board.Comment: Winning entry in the ABCD Neurocognitive Prediction Challenge at MICCAI 2019. 7 pages plus references, 3 figures, 1 tabl

A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei

Recent advances in magnetic resonance imaging methods, including data acquisition, pre-processing and analysis, have benefited research on the contributions of subcortical brain nuclei to human cognition and behavior. At the same time, these developments have led to an increasing need for a high-resolution probabilistic in vivo anatomical atlas of subcortical nuclei. In order to address this need, we constructed high spatial resolution, three-dimensional templates, using high-accuracy diffeomorphic registration of T_1- and T_2- weighted structural images from 168 typical adults between 22 and 35 years old. In these templates, many tissue boundaries are clearly visible, which would otherwise be impossible to delineate in data from individual studies. The resulting delineations of subcortical nuclei complement current histology-based atlases. We further created a companion library of software tools for atlas development, to offer an open and evolving resource for the creation of a crowd-sourced in vivoprobabilistic anatomical atlas of the human brain

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