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New tractography methods based on parametric models of white matter fibre dispersion

Diffusion weighted magnetic resonance imaging (DW-MRI) is a powerful imaging technique that can probe the complex structure of the body, revealing structural trends which exist at scales far below the voxel resolution. Tractography utilises the information derived from DW-MRI to examine the structure of white matter. Using information derived from DW-MRI, tractography can estimate connectivity between distinct, functional cortical and sub-cortical regions of grey matter. Understanding how seperate functional regions of the brain are connected as part of a network is key to understanding how the brain works. Tractography has been used to deliniate many known white matter structures and has also revealed structures not fully understood from anatomy due to limitations of histological examination. However, there still remain many shortcomings of tractography, many anatomical features for which tractography algorithms are known to fail, which leads to discrepancies between known anatomy and tractography results. With the aim of approaching a complete picture of the human connectome via tractography, we seek to address the shortcomings in current tractography techniques by exploiting new advances in modelling techniques used in DW-MRI, which provide more accurate representation of underlying white matter anatomy. This thesis introduces a methodology for fully utilising new tissue models in DWMRI to improve tractography. It is known from histology that there are regions of white matter where fibres disperse or curve rapidly at length scales below the DW-MRI voxel resolution. One area where dispersion is particularly prominent is the corona radiata. New DW-MRI models capture dispersion utilising specialised parametric probability distributions. We present novel tractography algorithms utilising these parametric models of dispersion in tractography to improve connectivity estimation in areas of dispersing fibres. We first present an algorithm utilising the the new parametric models of dispersion for tractography in a simple Bayesian framework. We then present an extension to this algorithm which introduces a framework to pool neighbourhood information from multiple voxels in the neighbournhood surrounding the tract in order to better estimate connectivity, introducing the new concept of the neighbourhood-informed orientation distribution function (NI-ODF). Specifically, using neighbourhood exploration we address the ambiguity arising in ’fanning polarity’. In regions of dispersing fibres, the antipodal symmetry inherent in DW-MRI makes it impossible to resolve the polarity of a dispersing fibre configuration from a local voxel-wise model in isolation, by pooling information from neighbouring voxels, we show that this issue can be addressed. We evaluate the newly proposed tractography methods using synthetic phantoms simulating canonical fibre configurations and validate the ability to effectively navigate regions of dispersing fibres and resolve fanning polarity. We then validate that the algorithms perform effectively in real in vivo data, using DW-MRI data from 5 healthy subjects. We show that by utilising models of dispersion, we recover a wider range of connectivity compared to other standard algorithms when tracking through an area of the brain known to have significant white fibre dispersion - the corona radiata. We then examine the impact of the new algorithm on global connectivity estimates in the brain. We find that whole brain connectivity networks derived using the new tractography method feature strong connectivity between frontal lobe regions. This is in contrast to networks derived using competing tractography methods which do not account for sub-voxel fibre dispersion. We also compare thalamo-cortical connectivity estimated using the newly proposed tractography method and compare with a compteing tractography method, finding that the recovered connectivity profiles are largely similar, with some differences in thalamo-cortical connections to regions of the frontal lobe. The results suggest that fibre dispersion is an important structural feature to model in the basis of a tractography algorithm, as it has a strong effect on connectivity estimation.