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

Age-related differences in the structural complexity of subcortical and ventricular structures

It has been well established that the volume of several subcortical structures decreases in relation to age. Different metrics of cortical structure (e.g., volume, thickness, surface area, and gyrification) have been shown to index distinct characteristics of interindividual differences; thus, it is important to consider the relation of age to multiple structural measures. Here, we compare age-related differences in subcortical and ventricular volume to those differences revealed with a measure of structural complexity, quantified as fractal dimensionality. Across 3 large data sets, totaling nearly 900 individuals across the adult lifespan (aged 18–94 years), we found greater age-related differences in complexity than volume for the subcortical structures, particularly in the caudate and thalamus. The structural complexity of ventricular structures was not more strongly related to age than volume. These results demonstrate that considering shape-related characteristics improves sensitivity to detect age-related differences in subcortical structures

Hemispheric Asymmetries in Cortical Thickness

Using magnetic resonance imaging and computational cortical pattern matching methods, we analyzed hemispheric differences in regional gray matter thickness across the lateral and medial cortices in young, healthy adults (n = 60). In addition, we investigated the influence of gender on the degree of thickness asymmetry. Results revealed global and regionally specific differences between the two hemispheres, with generally thicker cortex in the left hemisphere. Regions with significant leftward asymmetry were identified in the precentral gyrus, middle frontal, anterior temporal and superior parietal lobes, while rightward asymmetry was prominent in the inferior posterior temporal lobe and inferior frontal lobe. On the medial surface, significant rightward asymmetries were observed in posterior regions, while significant leftward asymmetries were evident from the vicinity of the paracentral gyrus extending anteriorly. Asymmetry profiles were similar in both sexes, but hemispheric differences appeared slightly pronounced in males compared with females, albeit a few regions also indicated greater asymmetry in females compared with males. Hemispheric differences in the thickness of the cortex might be related to hemisphere-specific functional specializations that are possibly related to behavioral asymmetrie

Towards Precision Psychiatry: gray Matter Development And Cognition In Adolescence

Precision Psychiatry promises a new era of optimized psychiatric diagnosis and treatment through comprehensive, data-driven patient stratification. Among the core requirements towards that goal are: 1) neurobiology-guided preprocessing and analysis of brain imaging data for noninvasive characterization of brain structure and function, and 2) integration of imaging, genomic, cognitive, and clinical data in accurate and interpretable predictive models for diagnosis, and treatment choice and monitoring. In this thesis, we shall touch on specific aspects that fit under these two broad points. First, we investigate normal gray matter development around adolescence, a critical period for the development of psychopathology. For years, the common narrative in human developmental neuroimaging has been that gray matter declines in adolescence. We demonstrate that different MRI-derived gray matter measures exhibit distinct age and sex effects and should not be considered equivalent, as has often been done in the past, but complementary. We show for the first time that gray matter density increases from childhood to young adulthood, in contrast with gray matter volume and cortical thickness, and that females, who are known to have lower gray matter volume than males, have higher density throughout the brain. A custom preprocessing pipeline and a novel high-resolution gray matter parcellation were created to analyze brain scans of 1189 youths collected as part of the Philadelphia Neurodevelopmental Cohort. This work emphasizes the need for future studies combining quantitative histology and neuroimaging to fully understand the biological basis of MRI contrasts and their derived measures. Second, we use the same gray matter measures to assess how well they can predict cognitive performance. We train mass-univariate and multivariate models to show that gray matter volume and density are complementary in their ability to predict performance. We suggest that parcellation resolution plays a big role in prediction accuracy and that it should be tuned separately for each modality for a fair comparison among modalities and for an optimal prediction when combining all modalities. Lastly, we introduce rtemis, an R package for machine learning and visualization, aimed at making advanced data analytics more accessible. Adoption of accurate and interpretable machine learning methods in basic research and medical practice will help advance biomedical science and make precision medicine a reality