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

Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction.

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome

Geometry Processing of Conventionally Produced Mouse Brain Slice Images

Brain mapping research in most neuroanatomical laboratories relies on conventional processing techniques, which often introduce histological artifacts such as tissue tears and tissue loss. In this paper we present techniques and algorithms for automatic registration and 3D reconstruction of conventionally produced mouse brain slices in a standardized atlas space. This is achieved first by constructing a virtual 3D mouse brain model from annotated slices of Allen Reference Atlas (ARA). Virtual re-slicing of the reconstructed model generates ARA-based slice images corresponding to the microscopic images of histological brain sections. These image pairs are aligned using a geometric approach through contour images. Histological artifacts in the microscopic images are detected and removed using Constrained Delaunay Triangulation before performing global alignment. Finally, non-linear registration is performed by solving Laplace's equation with Dirichlet boundary conditions. Our methods provide significant improvements over previously reported registration techniques for the tested slices in 3D space, especially on slices with significant histological artifacts. Further, as an application we count the number of neurons in various anatomical regions using a dataset of 51 microscopic slices from a single mouse brain. This work represents a significant contribution to this subfield of neuroscience as it provides tools to neuroanatomist for analyzing and processing histological data.Comment: 14 pages, 11 figure

Optimizing automated preprocessing streams for brain morphometric comparisons across multiple primate species

INTRODUCTION

MR techniques have delivered images of brains from a wide array of species, ranging from invertebrates to birds to elephants and whales. However, their potential to serve as a basis for comparative brain morphometric investigations has rarely been tapped so far (Christidis and Cox, 2006; Van Essen & Dierker, 2007), which also hampers a deeper understanding of the mechanisms behind structural alterations in neurodevelopmental disorders (Kochunov et al., 2010). One of the reasons for this is the lack of computational tools suitable for morphometrci comparisons across multiple species. In this work, we aim to characterize this gap, taking primates as an example.

METHODS

Using a legacy dataset comprising MR scans from eleven species of haplorhine primates acquired on the same scanner (Rilling & Insel, 1998), we tested different automated processing streams, focusing on denoising and brain segmentation. Newer multi-species datasets are not currently available, so our experiments with this decade-old dataset (which had a very low signal-to-noise ratio by contemporary standards) can serve to highlight the lower boundary of the current possibilities of automated processing pipelines. After manual orientation into Talairach space, an automated bias correction was performed using CARET (Van Essen et al., 2001) before the brains were extracted with FSL BET (Smith, 2002; Fig. 1) and either smoothed by an isotropic Gaussian Kernel, FSL SUSAN (Smith, 1996), an anisotropic diffusion filter (Perona & Malik, 1990), an optimized Rician non-local means filter (Gaser & Coupé, 2010), or not at all (Fig. 2 & 3). Segmentation of the brains (Fig. 2 & 4) was performed separately by either FSL FAST (Zhang, 2001) without atlas priors, or using an Adaptive Maximum A Posteriori Approach (Rajapakse et al., 1997). Finally, the white matter surface was extracted with CARET, and inspected for anatomical and topological correctness. 

RESULTS

Figure 3 shows that noise reduction was generally necessary but, at least for these noisy data, anisotropic filtering (SUSAN, diffusion filter, Rician filter) provided little improvement over simple isotropic filtering. While several segmentations worked well in individual species, our focus was on cross-species optimization of the processing pipeline, and none of the tested segmentations performed uniformly well in all 11 species. The performance could be improved by some of the denoising approaches and by deviating systematically from the default parameters recommended for processing human brains (cf. Fig. 4). Depending on the size of the brains and on the processing path, it took a double-core 2.4GHz iMac from about two minutes (squirrel monkeys) to half an hour (humans) to generate the white matter surface from the T1 image. Nonetheless, the resulting surfaces always necessitated topology correction and - often considerable - manual cleanup. 


CONCLUSIONS

Automated processing pipelines for surface-based morphometry still require considerable adaptations to reach optimal performance across brains of multiple species, even within primates (cf. Fig. 5). However, most contemporary datasets have a better signal-to-noise ratio than the ones used here, which provides for better segmentations and cortical surface reconstructions. Considering further that cross-scanner variability is well below within-species differences (Stonnington, 2008), the prospects look good for comparative evolutionary analyses of cortical parameters, and gyrification in particular. In order to succeed, however, computational efforts on comparative morphometry depend on high-quality imaging data from multiple species being more widely available.

ACKNOWLEDGMENTS

D.M, R.D, & C.G are supported by the German BMBF grant 01EV0709.


REFERENCES

Christidis, P & Cox, RW (2006), A Step-by-Step Guide to Cortical Surface Modeling of the Nonhuman Primate Brain Using FreeSurfer, Proc Human Brain Mapping Annual Meeting, http://afni.nimh.nih.gov/sscc/posters/file.2006-06-01.4536526043 .
Gaser, C & Coupé, P (2010), Impact of Non-local Means filtering on Brain Tissue Segmentation, OHBM 2010, Abstract 1770.
Kochunov, P & al. (2010), Mapping primary gyrogenesis during fetal development in primate brains: high-resolution in utero structural MRI study of fetal brain development in pregnant baboons, Frontiers in Neurogenesis, in press, DOI: 10.3389/fnins.2010.00020.
Perona, P & Malik J (1990), Scale space and edge detection using anisotropic diffusion, IEEE Trans Pattern Anal Machine Intell, vol. 12, no. 7, pp. 629-639.
Rajapakse, JC & al. (1997), Statistical approach to segmentation of single-channel cerebral MR images, IEEE Trans Med Imaging, vol. 16, no. 2, pp. 176-186.
Rilling, JK & Insel TR (1998), Evolution of the cerebellum in primates: differences in relative volume among monkeys, apes and humans. Brain Behav. Evol. 52, 308-314 doi:10.1159/000006575. Dataset available at http://www.fmridc.org/f/fmridc/77.html .
Smith, SM (1996), Flexible filter neighbourhood designation, Proc. 13th Int. Conf. on Pattern Recognition, vol. 1, pp. 206-212.
Smith, SM (2002), Fast robust automated brain extraction, Hum Brain Mapp, vol. 17, no. 3, pp. 143-155.
Stonnington, CM & al. (2008), Interpreting scan data acquired from multiple scanners: a study with Alzheimers disease, Neuroimage, vol. 39, no. 3, pp. 1180-1185.
Van Essen, DC & al. (2001), An Integrated Software System for Surface-based Analyses of Cerebral Cortex, J Am Med Inform Assoc, vol. 8, no. 5, pp. 443-459.
Van Essen, DC & Dierker DL (2007), Surface-based and probabilistic atlases of primate cerebral cortex, Neuron, vol. 56, no. 2, pp. 209-225.
Zhang, Y & al. (2001), Segmentation of brain MR images through a hidden Markov random field model and the expectation maximization algorithm, IEEE Trans Med Imaging, vol. 20, no. 1, pp. 45-57.
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Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

Learning and comparing functional connectomes across subjects

Functional connectomes capture brain interactions via synchronized fluctuations in the functional magnetic resonance imaging signal. If measured during rest, they map the intrinsic functional architecture of the brain. With task-driven experiments they represent integration mechanisms between specialized brain areas. Analyzing their variability across subjects and conditions can reveal markers of brain pathologies and mechanisms underlying cognition. Methods of estimating functional connectomes from the imaging signal have undergone rapid developments and the literature is full of diverse strategies for comparing them. This review aims to clarify links across functional-connectivity methods as well as to expose different steps to perform a group study of functional connectomes