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Introduction
Development of novel image processing algorithms for neuroscientific analysis of diffusion Magnetic Resonance Imaging data
Developer of the MRtrix3 software package: mrtrix.org
Current institution
Additional affiliations
April 2016 - present
April 2013 - April 2016
May 2009 - February 2013
Education
February 2004 - December 2008
February 2004 - December 2008
Publications
Publications (96)
Resective neurosurgery is a cornerstone treatment for many neurological conditions. Although traditionally viewed as localised procedure, increasing evidence from advanced magnetic resonance imaging (MRI) shows that also non-resected anatomy can degenerate following surgery. The relationship between local tissue removal and these postoperative chan...
Local connectivity analyses in fMRI such as the Vogt-Bailey Index, investigate the prevalence of co-fluctuations in the time-series of adjacent voxels. While there have been in silico assessments of the VB Index, this technique has not yet been assessed in vivo . This study has two aims: first, to assess the VB Index using a task paradigm with well...
Background
Inter-individual variability in neurobiological and clinical characteristics in mental illness is often overlooked by classical group-mean case-control studies. Studies using normative modelling to infer person-specific deviations of grey matter volume have indicated that group means are not representative of most individuals. The extent...
Eigenmodes can be derived from various structural brain properties, including cortical surface geometry ¹ and interareal axonal connections comprising an organism’s connectome ² . Pang and colleagues map geometric and connectome eigenmodes to spatial patterns of human brain activity, assessing whether brain connectivity or geometry provide greater...
The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some...
Diffusion MRI has provided insight into the widespread structural connectivity changes that characterize epilepsies. Although syndrome-specific white matter abnormalities have been demonstrated, studies to date have predominantly relied on statistical comparisons between patient and control groups. For diffusion MRI techniques to be of clinical val...
The network-based statistic (NBS) is a popular method for performing edge-wise statistical inference on brain networks, with a known limitation in the form of a need for the user to pre-define an arbitrary cluster-forming threshold. Recently a new method, the “Threshold Free Network Based Statistic” (TFNBS), was proposed to attempt to overcome this...
Diffusion MRI data are known to be sensitive to scanner and site effects, for which harmonization methods have been developed. However, harmonization methods have not yet been applied to many advanced diffusion imaging metrics. In this work, we apply the ComBat harmonization approach to fixel-based analysis. ComBat successfully minimizes scanner-re...
We mapped functional and structural brain networks for more than 40,000 UK Biobank participants. Structural connectivity was estimated with tractography and diffusion MRI. Resting-state functional MRI was used to infer regional functional connectivity. We provide high-quality structural and functional connectomes for multiple parcellation granulari...
Being on the bleeding edge of research requires the use of new and regularly updated software. The result is the occasional and inevitable occurrence of bugs. In the following work we present a case study where a feature request introduced a bug in a neuroimaging software package, which had consequences for the quality of results in a published art...
The Brain Imaging Data Structure (BIDS) has become an invaluable tool for standardizing the storage of neuroimaging data. This facilitates data sharing across neuroimaging projects (including using major archives such as OpenNeuro), and large-scale automated data processing using BIDS Apps (including major processing platforms such as brainlife.io)...
Recent developments in semi-global tractogram optimisation algorithms have opened the field of diffusion magnetic resonance imaging (MRI) to the possibility of performing quantitative assessment of structural fibre ‘connectivity’. The proper application of these methods in neuroscience research has, however, been limited by a lack of awareness, und...
File formats that store the results of computational tractography were typically developed within specific software packages. This approach has facilitated a myriad of applications, but this development approach has generated insularity within software packages, and has limited standardization. Moreover, because tractography file formats were devel...
Diffusion magnetic resonance imaging (dMRI) tractography is an advanced imaging technique that enables in vivo reconstruction of the brain’s white matter connections at macro scale. It provides an important tool for quantitative mapping of the brain’s structural connectivity using measures of connectivity or tissue microstructure. Over the last two...
Structural connectomes are increasingly mapped at high spatial resolutions comprising many hundreds-if not thousands-of network nodes. However, high-resolution connectomes are particularly susceptible to image registration misalignment, tractography artifacts, and noise, all of which can lead to reductions in connectome accuracy and test-retest rel...
Structural connectomes are increasingly mapped at high spatial resolutions comprising many hundreds—if not thousands—of network nodes. However, high-resolution connectomes are particularly susceptible to image registration misalignment, tractography artifacts, and noise, all of which can lead to reductions in connectome accuracy and test-retest rel...
While the Fixel-Based Analysis (FBA) framework provides familywise error control across a whole-brain template accounting for the presence of crossing fibres in the white matter, its typical usage fails to correct for multiple hypothesis tests due to the utilisation of multiple quantitative metrics. We demonstrate different methods that can be empl...
Diffusion magnetic resonance imaging (dMRI) tractography is an advanced imaging technique that enables in vivo mapping of the brain's white matter connections at macro scale. Over the last two decades, the study of brain connectivity using dMRI tractography has played a prominent role in the neuroimaging research landscape. In this paper, we provid...
“Tractography” refers to the process of digitally reconstructing the spatial trajectories of elongated thin structures based on a continuous field of local orientation data; most commonly in reference to white matter axons within the central nervous system based on a diffusion Magnetic Resonance Imaging (MRI) model. This technology provides a uniqu...
The diffusion tensor model for diffusion MRI has been used extensively to study asymmetry in the human brain white matter. However, given the limitations of the tensor model, the nature of any underlying asymmetries remains uncertain, particularly in crossing fibre regions. Here, we provide a more robust characterization of human brain white matter...
The aim of the current study was to longitudinally examine how adrenarcheal hormones influence the development of white matter structure from age 8.5 to 10 years. Participants were 120 children (66 female; mean age 8.45 years at Time 1 and 9.97 years at Time 2) who completed two diffusion-weighted imaging scans 1.5 years apart. Morning saliva sampl...
Alzheimer’s disease (AD) is characterised by degeneration of specific white matter tracts, however the longitudinal trajectory of tract-specific decline has not yet been well described. In this work, we utilise a longitudinal fixel-based analysis framework to investigate specific fibre tracts that exhibit accelerated decline in AD and mild cognitiv...
Head motion is a major confounding factor in neuroimaging studies. While numerous studies have investigated how motion impacts estimates of functional connectivity, the effects of motion on structural connectivity measured using diffusion MRI have not received the same level of attention, despite the fact that, like functional MRI, diffusion MRI re...
Recent developments in semi-global tractogram optimisation algorithms have opened the field of diffusion MRI to the possibility of performing quantitative assessment of structural fibre connectivity. The proper application of these methods in neuroscience research has however been limited by a lack of awareness, understanding, or appreciation for t...
Background
The brain's white matter undergoes profound changes during early childhood, which are believed to underlie the rapid development of cognitive and behavioral skills during this period. Neurite density, and complexity of axonal projections, have been shown to change across the life span, though changes during early childhood are poorly cha...
The brain's white matter undergoes profound changes during early childhood that are believed to underlie the rapid development of cognitive and behavioral skills across this period. Diffusion MRI estimates of axonal density and dispersion of axonal projections have been shown to increase with brain development. Widespread increases in estimated axo...
The "Anatomically-Constrained Tractography (ACT)" framework enhances the biological accuracy of diffusion MRI streamlines tractography reconstruction, by constraining the propagation and termination of streamlines based on tissue segmentation from a high-resolution, high-contrast anatomical image (e.g. T1-weighted).
The tissue segmentation image t...
Head motion is a major confounding factor in neuroimaging studies. While numerous studies have investigated how motion impacts estimates of functional connectivity, the effects of motion on structural connectivity measured using diffusion MRI have not received the same level of attention, despite the fact that, like functional MRI, diffusion MRI re...
Early childhood is an important period for cognitive and brain development, though white matter changes specific to this period remain understudied. Here we utilize a novel analytic approach to quantify and track developmental changes in white matter micro- and macro-structure, calculated from individually oriented fiber-bundle populations, termed...
Endpoint-to-endpoint fibre bundle connectivity estimated using spherical deconvolution & streamlines tractography in diffusion MRI may be excessive in the presence of pathologies that involve truncation of axons within the white matter. Here we propose a simple modification to an existing method that directly quantifies and corrects for this over-e...
Background
The brain’s white matter undergoes profound changes during early childhood, which are believed to underlie the rapid development of cognitive and behavioral skills during this period. Neurite density, and complexity of axonal projections, have been shown to change across the life span, though changes during early childhood are poorly cha...
MRtrix3 is an open-source, cross-platform software package for medical image processing, analysis and visualisation, with a particular emphasis on the investigation of the brain using diffusion MRI. It is implemented using a fast, modular and flexible general-purpose code framework for image data access and manipulation, enabling efficient developm...
The Fixel-Based Analysis (FBA) framework enables data-driven statistical inference of effects in diffusion MRI measures that is both sensitive and specific to crossing fibre geometry ("fixel": specific fibre bundle element within a specific voxel). A fundamental building block of this framework is the Connectivity-based Fixel Enhancement (CFE) meth...
Dravet Syndrome is a devastating form of Epilepsy involving infantile seizures and slowing of development after the first year of life. Unlike conventional brain imaging, which shows little evidence of abnormality in these subjects, advanced diffusion MRI analysis based on Constrained Spherical Deconvolution - possessing both sensitivity and specif...
Early childhood is a period of profound cognitive maturation believed to be related to changes in white matter. Previous diffusion tensor imaging (DTI) studies have shown how white matter tracts mature throughout the lifespan, though few have focused specifically on early childhood. Furthermore, while lifespan development of fractional anisotropy (...
Fixel-Based Analysis (FBA) enables robust whole-brain statistical analysis of both microscopic and macroscopic white matter properties that is both sensitive and specific to crossing fibre geometry. Given the influence of macroscopic brain differences in such experiments, interest has been expressed in how best to account for variations in brain vo...
Early childhood is an important period for cognitive and brain development, though white matter changes specific to this period remain understudied. Here we utilize a novel analytic approach to quantify and track longitudinal changes in white matter micro- and macro-structure, calculated from individually oriented fiber-bundle populations, termed '...
When using diffusion MRI streamlines tractograms to construct structural connectomes, ideally, each streamline should connect exactly 2 regions-of-interest (i.e. network nodes) as defined by a given brain parcellation scheme. However, the ill-posed nature of termination criteria in many tractography algorithms can cause streamlines apparently being...
Fixel-Based Analysis (FBA) enables data-driven statistical inference on quantitative white matter measures derived from diffusion MRI with both sensitivity and specificity to crossing fibre bundle geometry ("fixel": specific fibre bundle element within a specific voxel). This framework relies on spatial normalisation of participant data to a templa...
Robust and accurate reconstruction of the macroscopic brain structural connectome from diffusion MRI data requires a large number of image processing and digital reconstruction steps. The complexity of such tasks, and the daunting nature of installing and adequately learning one or more neuroimaging software packages, may limit the uptake of state-...
Recent advances in diffusion MRI tractography permit the generation of dense weighted structural connectomes that offer greater insight into brain organization. However, these efforts are hampered by the lack of consensus on how to extract topological measures from the resulting graphs. Here we evaluate the common practice of removing the graphs’ w...
MRtrix3 is an open-source, cross-platform software package for medical image processing, analysis and visualization, with a particular emphasis on the investigation of the brain using diffusion MRI. It is implemented using a fast, modular and flexible general-purpose code framework for image data access and manipulation, enabling efficient developm...
Recent advances in diffusion MRI tractography permit the generation of dense weighted structural connectomes that offer greater insight into brain organization. However, these efforts are hampered by the lack of consensus on how to extract topological measures from the resulting graphs. Here we evaluate the common practice of removing the graphs’ w...
Differences in brain networks and underlying white matter abnormalities have been suggested to underlie symptoms of autism spectrum disorder (ASD). However, robustly characterizing microstructural white matter differences has been challenging. In the present study, we applied an analytic technique that calculates structural metrics specific to diff...
White matter fibre development in childhood involves dynamic changes to microstructural organisation driven by increasing axon diameter, density, and myelination. However, there is a lack of longitudinal studies that have quantified advanced diffusion metrics to identify regions of accelerated fibre maturation, particularly across the early puberta...
This study systematically investigates a fundamental question for tractogram- based connectomics research: for a given resolution of brain parcellation, how many streamlines are required for reproducible connectome construction? We incorporate state-of-the-art tractography techniques with surface parcellation schemes of multiple granularities to in...
Purpose: White matter fibre development in childhood involves dynamic changes to microstructural organisation driven by increasing axon diameter, density, and myelination. However, there is a lack of longitudinal studies that have quantified advanced diffusion metrics to identify regions of accelerated fibre maturation, particularly across the earl...
A growing number of studies have identified that relative early/late onset of puberty can lead to differential patterns of microstructural white matter development. The aim of this study was to investigate the longitudinal development of white matter properties using fixel-based analysis (FBA), a method that estimates the microscopic density and ma...
Early childhood is a period of profound white matter maturation, as reflected by developmental changes in diffusion-tensor derived metrics such as fractional anisotropy and mean diffusivity. These metrics are non-specific however, and are unreliable in regions of crossing and kissing fibers. Higher-order diffusion models and biologically more relev...
A requisite step in performing a Fixel-Based Analysis (FBA) is the determination of "fixel correspondence", which defines how discrete fibre elements (fixels) for a particular subject map to the fixels defined in each voxel in template space. The method used thus far for this purpose - simply selecting the subject fixel that best aligns with the te...
Interest in the study of brain connectivity is growing, particularly in understanding the dynamics of the structural/functional connectivity relation. Structural and functional connectivity are most often analysed independently of each other. Track-weighted functional connectivity (TW-FC) was recently proposed as a means to combine structural/funct...
Purpose:
To investigate whether diffusion MRI can be used to study cortical segregation based on a contrast related to neurite density, thus providing a complementary tool to myelin-based MRI techniques used for myeloarchitecture.
Methods:
Several myelin-sensitive MRI methods (e.g., based on T1 , T2 , and T2*) have been proposed to parcellate co...
Synopsis Rich-club organizations, characterizing the higher-level topology of the brain network, has been commonly identií³ed from structural connectomes constructed using DTI based on network degrees. This analysis can however be compromised by the following issues: (i) DTI limitations in resolving crossing-í³bers; and (ii) the original degree...
Neuroimaging studies assessing white and grey matter are most typically performed as independent analyses. The relationships between white and grey matter abnormalities are therefore poorly understood. We present a novel framework for interrogating relationships between quantitative measures derived from grey matter analysis, and diffusion MRI-base...
Apparent Fibre Density (AFD) is a measure derived from un-normalised fibre orientation distributions. To make AFD quantitative across subjects, images need to be intensity normalised and bias field corrected. Here we present a fast and robust approach to simultaneous bias field correction and intensity normalisation by exploiting tissue compartment...
This study introduces a novel diffusion MRI streamlines tractography framework called mesh-based anatomically-constrained tractography (MACT) that incorporates high-resolution surface models of various brain tissues as more accurate anatomical constraints in the fibre-tracking process. By detecting intersections between streamlines and tissue surfa...
The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and d...
The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and d...
Voxel-based analysis of diffusion MRI data is increasingly popular. However, most white matter voxels contain contributions from multiple fibre populations (often referred to as crossing fibres), and therefore voxel-averaged quantitative measures (e.g. fractional anisotropy) are not fibre-specific and have poor interpretability. Using higher-order...
Estimation of an appropriate response function for spherical deconvolution is commonly performed using the image data itself, by the following steps: 1. Use some heuristic process to select a subset of white matter voxels considered to contain a single fibre population. 2. Re-orient the diffusion signal in each voxel so that the estimated fibre ori...
Diffusion MRI streamlines tractography is the main in vivo technique for inferring structural brain connectivity. Ideally, during structural connectome construction, each streamline should connect exactly 2 brain regions-of-interest (i.e. network nodes); the efficacy of identifying such 'pairwise' connectivity has however been shown to be heavily a...
This study highlights the issue of using the common strategy for assigning individual streamlines to an atlas-based brain parcellation. This process is non-trivial and can introduce ambiguity into connectome quantification. In many fibre-tracking algorithms, track termination criteria can cause premature termination of streamlines within WM or CSF,...
The human connectome is a topologically complex, spatially embedded network. While its topological properties have been richly characterized, the constraints imposed by its spatial embedding are poorly understood. By applying a novel resampling method to tractography data, we show that the brain's spatial embedding makes a major, but not definitive...
Diffusion weighted imaging (DWI) acquisitions typically suffer from a lower spatial resolution, compared to their T1 structural counterparts, but provide unique angular information. Researchers and clinical users may often find themselves switching back and forth between the "traditional" directionally-encoded colour (DEC) FA map and a T1 map to na...
The "traditional" directionally-encoded colour (DEC) FA map is an icon of DTI, but is also affected by its inherent flaws. The first eigenvector is known to be ill-defined in regions of crossing fibres, resulting in misleading specific DEC values as well as "false edges" in the overall map. Additionally, the FA shows naturally low values in these r...
A biological parameter that would be valuable to be able to extract from diffusion MRI data is the local white matter axonal density. Track-density imaging (TDI) has been used as if it could provide such a measure; however, this has been the subject of controversy, primarily due to the fact that track-count quantitation is highly sensitive to track...
In brain regions containing crossing fibre bundles, voxel-average diffusion MRI measures such as Fractional Anisotropy (FA) are difficult to interpret, and lack within-voxel single fibre population specificity. Recent work has focused on the development of more interpretable quantitative measures that can be associated with a specific fibre populat...
Target Audience: Researchers interested in direct inference of group differences in structural or functional connectivity matrices. Introduction: The structural and functional connectivity of the brain is increasingly being interrogated using the framework of the connectome, where connections between pre-defined regions of grey matter are represent...
The connectome framework is an increasingly popular method of interrogating functional and structural brain connectivity. In population studies, statistical inference at individual connection level lacks power due to the multiple comparisons problem. The NetworkBased Statistic (NBS)(Zalesky 2010) method was introduced to address this issue, utiliz...
Fixel-based morphometry is a novel method for whole-brain white matter morphometry that gives fibre tract-specific information in voxels with crossing fibres.
Recently several novel image contrasts derived from whole-brain fibre tracking-data (tractograms) have been introduced. The novel contrasts of these track-weighted imaging (TWI) methods may provide important information for clinical neuroscience studies. However, before they can be used reliably to generate quantitative measures, it is important to...
MRI provides a powerful tool for studying the functional and structural connections in the brain non-invasively. The technique of functional connectivity (FC) exploits the intrinsic temporal correlations of slow spontaneous signal fluctuations to characterise brain functional networks. In addition, diffusion MRI fibre-tracking can be used to study...
Track-density imaging (TDI) was recently introduced as a method to achieve super-resolution imaging using whole-brain fibre-tracking data (the so called tractogram). A similar approach to achieve super-resolution was later applied for average pathlength mapping (APM). These two methods have in common that the tractogram information is used to creat...
