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

Intensity Segmentation of the Human Brain with Tissue dependent Homogenization

High-precision segmentation of the human cerebral cortex based on T1-weighted MRI is still a challenging task. When opting to use an intensity based approach, careful data processing is mandatory to overcome inaccuracies. They are caused by noise, partial volume effects and systematic signal intensity variations imposed by limited homogeneity of the acquisition hardware. We propose an intensity segmentation which is free from any shape prior. It uses for the first time alternatively grey (GM) or white matter (WM) based homogenization. This new tissue dependency was introduced as the analysis of 60 high resolution MRI datasets revealed appreciable differences in the axial bias field corrections, depending if they are based on GM or WM. Homogenization starts with axial bias correction, a spatially irregular distortion correction follows and finally a noise reduction is applied. The construction of the axial bias correction is based on partitions of a depth histogram. The irregular bias is modelled by Moody Darken radial basis functions. Noise is eliminated by nonlinear edge preserving and homogenizing filters. A critical point is the estimation of the training set for the irregular bias correction in the GM approach. Because of intensity edges between CSF (cerebro spinal fluid surrounding the brain and within the ventricles), GM and WM this estimate shows an acceptable stability. By this supervised approach a high flexibility and precision for the segmentation of normal and pathologic brains is gained. The precision of this approach is shown using the Montreal brain phantom. Real data applications exemplify the advantage of the GM based approach, compared to the usual WM homogenization, allowing improved cortex segmentation

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

Method for bias field correction of brain T1-weighted magnetic resonance images minimizing segmentation error

This work presents a new algorithm (nonuniform intensity correction; NIC) for correction of intensity inhomogeneities in T1-weighted magnetic resonance (MR) images. The bias field and a bias-free image are obtained through an iterative process that uses brain tissue segmentation. The algorithm was validated by means of realistic phantom images and a set of 24 real images. The first evaluation phase was based on a public domain phantom dataset, used previously to assess bias field correction algorithms. NIC performed similar to previously described methods in removing the bias field from phantom images, without introduction of degradation in the absence of intensity inhomogeneity. The real image dataset was used to compare the performance of this new algorithm to that of other widely used methods (N3, SPM'99, and SPM2). This dataset included both low and high bias field images from two different MR scanners of low (0.5 T) and medium (1.5 T) static fields. Using standard quality criteria for determining the goodness of the different methods, NIC achieved the best results, correcting the images of the real MR dataset, enabling its systematic use in images from both low and medium static field MR scanners. A limitation of our method is that it might fail if the bias field is so high that the initial histogram does not show bimodal distribution for white and gray matterPublicad

Towards in vivo g-ratio mapping using MRI: unifying myelin and diffusion imaging

The g-ratio, quantifying the comparative thickness of the myelin sheath encasing an axon, is a geometrical invariant that has high functional relevance because of its importance in determining neuronal conduction velocity. Advances in MRI data acquisition and signal modelling have put in vivo mapping of the g-ratio, across the entire white matter, within our reach. This capacity would greatly increase our knowledge of the nervous system: how it functions, and how it is impacted by disease. This is the second review on the topic of g-ratio mapping using MRI. As such, it summarizes the most recent developments in the field, while also providing methodological background pertinent to aggregate g-ratio weighted mapping, and discussing pitfalls associated with these approaches. Using simulations based on recently published data, this review demonstrates the relevance of the calibration step for three myelin-markers (macromolecular tissue volume, myelin water fraction, and bound pool fraction). It highlights the need to estimate both the slope and offset of the relationship between these MRI-based markers and the true myelin volume fraction if we are really to achieve the goal of precise, high sensitivity g-ratio mapping in vivo. Other challenges discussed in this review further evidence the need for gold standard measurements of human brain tissue from ex vivo histology. We conclude that the quest to find the most appropriate MRI biomarkers to enable in vivo g-ratio mapping is ongoing, with the potential of many novel techniques yet to be investigated.Comment: Will be published as a review article in Journal of Neuroscience Methods as parf of the Special Issue with Hu Cheng and Vince Calhoun as Guest Editor

Test-retest reliability of structural brain networks from diffusion MRI

Structural brain networks constructed from diffusion MRI (dMRI) and tractography have been demonstrated in healthy volunteers and more recently in various disorders affecting brain connectivity. However, few studies have addressed the reproducibility of the resulting networks. We measured the test–retest properties of such networks by varying several factors affecting network construction using ten healthy volunteers who underwent a dMRI protocol at 1.5 T on two separate occasions. Each T1-weighted brain was parcellated into 84 regions-of-interest and network connections were identified using dMRI and two alternative tractography algorithms, two alternative seeding strategies, a white matter waypoint constraint and three alternative network weightings. In each case, four common graph-theoretic measures were obtained. Network properties were assessed both node-wise and per network in terms of the intraclass correlation coefficient (ICC) and by comparing within- and between-subject differences. Our findings suggest that test–retest performance was improved when: 1) seeding from white matter, rather than grey; and 2) using probabilistic tractography with a two-fibre model and sufficient streamlines, rather than deterministic tensor tractography. In terms of network weighting, a measure of streamline density produced better test–retest performance than tract-averaged diffusion anisotropy, although it remains unclear which is a more accurate representation of the underlying connectivity. For the best performing configuration, the global within-subject differences were between 3.2% and 11.9% with ICCs between 0.62 and 0.76. The mean nodal within-subject differences were between 5.2% and 24.2% with mean ICCs between 0.46 and 0.62. For 83.3% (70/84) of nodes, the within-subject differences were smaller than between-subject differences. Overall, these findings suggest that whilst current techniques produce networks capable of characterising the genuine between-subject differences in connectivity, future work must be undertaken to improve network reliability