Diffusion Tensor Imaging Biomarkers of Brain Development and Disease

<p>Understanding the structure of the brain has been a major goal of neuroscience research over the past century, driven in part by the understanding that brain structure closely follows function. Normative brain maps, or atlases, can be used to understand normal brain structure, and to identify structural differences resulting from disease. Recently, diffusion tensor magnetic resonance imaging has emerged as a powerful tool for brain atlasing; however, its utility is hindered by image resolution and signal limitations. These limitations can be overcome by imaging fixed ex-vivo specimens stained with MRI contrast agents, a technique known as diffusion tensor magnetic resonance histology (DT-MRH). DT-MRH represents a unique, quantitative tool for mapping the brain with unprecedented structural detail. This technique has engendered a new generation of 3D, digital brain atlases, capable of representing complex dynamic processes such as neurodevelopment. This dissertation explores the use of DT-MRH for quantitative brain atlasing in an animal model and initial work in the human brain. </p><p>Chapter 1 describes the advantages of the DT-MRH technique, and the motivations for generating a quantitative atlas of rat postnatal neurodevelopment. The second chapter covers optimization of the DT-MRH hardware and pulse sequence design for imaging the developing rat brain. Chapter 3 details the acquisition and curation of rat neurodevelopmental atlas data. Chapter 4 describes the creation and implementation of an ontology-based segmentation scheme for tracking changes in the developing brain. Chapters 5 and 6 pertain to analyses of volumetric changes and diffusion tensor parameter changes throughout rat postnatal neurodevelopment, respectively. Together, the first six chapters demonstrate many of the unique and scientifically valuable features of DT-MRH brain atlases in a popular animal model.</p><p>The final two chapters are concerned with translating the DT-MRH technique for use in human and non-human primate brain atlasing. Chapter 7 explores the validity of assumptions imposed by DT-MRH in the primate brain. Specifically, it analyzes computer models and experimental data to determine the extent to which intravoxel diffusion complexity exists in the rhesus macaque brain, a close model for the human brain. Finally, Chapter 8 presents conclusions and future directions for DT-MRH brain atlasing, and includes initial work in creating DT-MRH atlases of the human brain. In conclusion, this work demonstrates the utility of a DT-MRH brain atlasing with an atlas of rat postnatal neurodevelopment, and lays the foundation for creating a DT-MRH atlas of the human brain.</p>Dissertatio

Interoperable atlases of the human brain

International audienceThe last two decades have seen an unprecedented development of human brain mapping approaches at various spatial and temporal scales. Together, these have provided a large fundus of information on many different as-pects of the human brain including micro-and macrostructural segregation, regional specialization of function, connectivity, and temporal dynamics. Atlases are central in order to integrate such diverse information in a topo-graphically meaningful way. It is noteworthy, that the brain mapping field has been developed along several major lines such as structure vs. function, postmortem vs. in vivo, individual features of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to understand human brain organization, however, it seems inevitable that these different lines are integrated and combined into a multimodal human brain model. To this aim, we held a workshop to determine the constraints of a multi-modal human brain model that are needed to enable (i) an integration of different spatial and temporal scales and data modalities into a common reference system, and (ii) efficient data exchange and analysis. As detailed in this report, to arrive at fully interoperable atlases of the human brain will still require much work at the frontiers of data acquisition, analysis, and represen-tation. Among them, the latter may provide the most challenging task, in particular when it comes to representing features of vastly different scales of space, time and abstraction. The potential benefits of such endeavor, however, clearly outweigh the problems, as only such kind of multi-modal human brain atlas may provide a starting point from which the complex relationships between structure, function, and connectivity may be explored

Full-field MRI measurements of in-vivo positional brain shift reveal the significance of intra-cranial geometry and head orientation for stereotactic surgery

Positional brain shift (PBS), the sagging of the brain under the effect of gravity, is comparable in magnitude to the margin of error for the success of stereotactic interventions (∼ 1 mm). This non-uniform shift due to slight differences in head orientation can lead to a significant discrepancy between the planned and the actual location of surgical targets. Accurate in-vivo measurements of this complex deformation are critical for the design and validation of an appropriate compensation to integrate into neuronavigational systems. PBS arising from prone-to-supine change of head orientation was measured with magnetic resonance imaging on 11 young adults. The full-field displacement was extracted on a voxel-basis via digital volume correlation and analysed in a standard reference space. Results showed the need for target-specific correction of surgical targets, as a significant displacement ranging from 0.52 to 0.77 mm was measured at surgically relevant structures. Strain analysis further revealed local variability in compressibility: anterior regions showed expansion (both volume and shape change), whereas posterior regions showed small compression, mostly dominated by shape change. Finally, analysis of correlation demonstrated the potential for further patient- and intervention-specific adjustments, as intra-cranial breadth and head tilt correlated with PBS reaching statistical significance

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

The Developing Human Connectome Project: a minimal processing pipeline for neonatal cortical surface reconstruction

The Developing Human Connectome Project (dHCP) seeks to create the first 4-dimensional connectome of early life. Understanding this connectome in detail may provide insights into normal as well as abnormal patterns of brain development. Following established best practices adopted by the WU-MINN Human Connectome Project (HCP), and pioneered by FreeSurfer, the project utilises cortical surface-based processing pipelines. In this paper, we propose a fully automated processing pipeline for the structural Magnetic Resonance Imaging (MRI) of the developing neonatal brain. This proposed pipeline consists of a refined framework for cortical and sub-cortical volume segmentation, cortical surface extraction, and cortical surface inflation, which has been specifically designed to address considerable differences between adult and neonatal brains, as imaged using MRI. Using the proposed pipeline our results demonstrate that images collected from 465 subjects ranging from 28 to 45 weeks post-menstrual age (PMA) can be processed fully automatically; generating cortical surface models that are topologically correct, and correspond well with manual evaluations of tissue boundaries in 85% of cases. Results improve on state-of-the-art neonatal tissue segmentation models and significant errors were found in only 2% of cases, where these corresponded to subjects with high motion. Downstream, these surfaces will enhance comparisons of functional and diffusion MRI datasets, supporting the modelling of emerging patterns of brain connectivity