bioRxiv Science⌕ Search

Biology subjects

Tournier, J.-D.

Publications and source records attributed to Tournier, J.-D..

15 recordsLinked to original sources

Thalamocortical constraints on areal connectivity in the developing human brain

The thalamus plays a central role in cortical development, organisation and function. Thalamic nuclei acquire distinct molecular identities during gestation, with first-order relays maturing before higher-order nuclei. Thalamic afferents innervate the cortical plate with a precise order, disruptions to which alter cortical function. Recent models propose that thalamic input to primary sensory cortex constrains the development of wider cortical networks, promoting the formation of highly-connected hubs in association cortex. Here, we combine neuroimaging, post mortem gene expression data and network modelling to examine how the timing and spatial distribution of thalamocortical innervation influences the formation of cortical networks during gestation. We find that the maturation rates of thalamic nuclei align with predicted timing and distribution of afferent outgrowth. While higher order nuclei connect widely across the cortex, they do not preferentially target high-degree hubs. Instead, hubs emerge from interdependent spatiotemporal constraints imposed by both wiring distance and thalamocortical maturation.

neuroscience↗

TRAMFIX: TRavelling Across Melbourne for FIXel-based analysis (a reproducibility study)

Fixel-based analysis (FBA) has gained substantial interest for its ability to probe fibre-specific changes in the brains white matter from diffusion-weighted imaging data. However, the reproducibility and reliability of fixel-based measures across different scanners remains largely unknown. In this work, we present TRAMFIX: a multisite dataset of travelling participants (n=10 healthy adults) scanned across four 3T MRI scanners using a harmonised multi-shell DWI protocol. DWI data were processed using two pipelines that can adopted when performing multi-site FBA studies (site-specific versus pooled processing). We extracted fixel-based measures of fibre density (FD), fibre cross-section (FC), and fibre density and cross-section (FDC), as well as diffusion tensor imaging (DTI)-based fractional anisotropy (FA) and mean diffusivity (MD) from the harmonised protocol. Within-subject coefficients of variation (CVws) and intraclass correlation coefficients (ICC) of FBA and DTI measures were computed at multiple resolutions of computation and analysis: (i) the whole-brain averaged level, (ii) tract-level, and (iii) fixel- or voxel-level. Fixel-based metrics demonstrated high reproducibility and reliability at the whole-brain level (CVws ranging between 0.51% to 1.57% and ICC between 0.93 and 0.996). While reproducibility and reliability remained high for tract-averaged FBA measures (particularly the FC and FDC metrics), some tracts exhibited lower ICC values < 0.8 for the FD measure. When examining fixel-level reliability and reproducibility clear spatial patterns emerged, with lower ICC across subcortical and cerebellar regions, and higher CVws at the cortical boundaries. Across all levels, tensor-based metrics demonstrated slightly lower reproducibility and reliability metrics than FBA measures, suggesting that FBA metrics are just as, if not more, reproducible than DTI metrics across scanners when using identical protocols. Our findings provide support for the reproducibility and reliability of fixel-based measures, highlighting their potential for use in multi-site FBA studies. Future work examining protocol-related differences, as well as appropriate harmonisation strategies when pooling data across sites and scanners, will be valuable.

neuroscience↗

In vivo tractography of human neonatal white-matter pathways underlying hypothalamic and reward functions to study predispositions to neurodevelopmental conditions and obesity

White matter (WM) tracts of the reward, limbic, and autonomic systems implicate the hypothalamus, nucleus accumbens, ventral tegmental area and the amygdala and are associated with autism, ADHD, addiction and obesity. However, since most of these structures remain uncharacterised in vivo in human neonates, research on the early-life predispositions to these long-term "mind and body" conditions and the impact of common fetal exposures such as maternal obesity remains limited. Through the developing human connectome project, we acquired 3T brain diffusion and structural magnetic resonance imaging from healthy neonates born at-term to 137 normal-weight women (controls) and to 28 obese women and scanned at mean 40 weeks+6 days (+/-9 days) postmenstrual age (PMA). We first developed novel tractography protocols to reconstruct anatomical WM pathways for the neonatal medial forebrain bundle, ventral amygdalofugal pathway, amygdalo-accumbens fasciculus, stria terminalis and autonomic dorsal longitudinal fasciculus (DLF). We then quantified WM structure from the mean tract fibre bundle density (FD) and fibre cross-section (FC) and using regression path models evaluated WM change across PMA and the effects of antenatal obesity exposure and neonatal covariates. Lastly, we explored if neonatal WM FD and obesity exposure predicted child psycho-cognitive outcomes and anthropometry at 18 months. We show successful in vivo tractography of tracts with high topographical correspondence to adult histology, including in subcompartments of the hypothalamus and amygdala. The obesity exposure*PMA interaction was significant for mean FD in the bilateral amygdalo-accumbens fasciculus and right uncinate fasciculus. Males had larger FC in these same tracts bilaterally. Antenatal obesity exposure predicted lower cognitive scores and higher WHO weight and height z-scores at 18 months. Toddler reward-seeking temperament was correlated with higher weight zscore and was predicted by higher neonatal FD of the amygdalo-accumbens and uncinate fasciculi. Denser neonatal DLF predicted higher language and cognitive scores and fewer autistic traits at 18 months. In conclusion, we inform on neuroanatomical growth in vivo of discrete multisystemic regulatory networks and present evidence for early-life predispositions to psychological outcomes and obesity.

neuroscience↗

Dynamic changes in subplate and cortical plate microstructure precede the onset of cortical folding in vivo

Cortical gyrification takes place predominantly during the second to third trimester, alongside other fundamental developmental processes, such as the development of white matter connections, lamination of the cortex and formation of neural circuits. The mechanistic biology that drives the formation cortical folding patterns remains an open question in neuroscience. In our previous work, we modelled the in utero diffusion signal to quantify the maturation of microstructure in transient fetal compartments, identifying patterns of change in diffusion metrics that reflect critical neurobiological transitions occurring in the second to third trimester. In this work, we apply the same modelling approach to explore whether microstructural maturation of these compartments is correlated with the process of gyrification. We quantify the relationship between sulcal depth and tissue anisotropy within the cortical plate (CP) and underlying subplate (SP), key transient fetal compartments often implicated in mechanistic hypotheses about the onset of gyrification. Using in utero high angular resolution multi-shell diffusion-weighted imaging (HARDI) from the Developing Human Connectome Project (dHCP), our analysis reveals that the anisotropic, tissue component of the diffusion signal in the SP and CP decreases immediately prior to the formation of sulcal pits in the fetal brain. By back-projecting a map of folded brain regions onto the unfolded brain, we find evidence for cytoarchitectural differences between gyral and sulcal areas in the late second trimester, suggesting that regional variation in the microstructure of transient fetal compartments precedes, and thus may have a mechanistic function, in the onset of cortical folding in the developing human brain.

neuroscience↗

Spatiotemporal tissue maturation of thalamocortical pathways in the human fetal brain

The development of connectivity between the thalamus and maturing cortex is a fundamental process in the second half of human gestation, establishing the neural circuits that are the basis for several important brain functions. In this study, we acquired high-resolution in utero diffusion MRI from 140 fetuses as part of the Developing Human Connectome Project, to examine the emergence of thalamocortical white matter over the second to third trimester. We delineate developing thalamocortical pathways and parcellate the fetal thalamus according to its cortical connectivity using diffusion tractography. We then quantify microstructural tissue components along the tracts in the fetal compartments that are critical substrates for white matter maturation, such as the subplate and intermediate zone. We identify patterns of change in the diffusion metrics that reflect critical neurobiological transitions occurring in the second to third trimester, such as the disassembly of radial glial scaffolding and the lamination of the cortical plate. These maturational trajectories of MR signal in transient fetal compartments provide a normative reference to complement histological knowledge, facilitating future studies to establish how developmental disruptions in these regions contribute to pathophysiology.

neuroscience↗

Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age

IntroductionThe dynamic nature and complexity of the cellular events that take place during the last trimester of pregnancy make the developing cortex particularly vulnerable to perturbations. Abrupt interruption to normal gestation can lead to significant deviations to many of these processes, resulting in atypical trajectory of cortical maturation in preterm birth survivors. MethodsWe sought to first map typical cortical micro and macrostructure development using invivo MRI in a large sample of healthy term-born infants scanned after birth (n=270). Then we offer a comprehensive characterisation of the cortical consequences of preterm birth in 78 preterm infants scanned at term-equivalent age (37-44 weeks postmenstrual age). We describe the group-average atypicality, the heterogeneity across individual preterm infants, and relate individual deviations from normative development to age at birth and neurodevelopment at 18 months. ResultsIn the term-born neonatal brain, we observed regionally specific age-associated changes in cortical morphology and microstructure, including rapid surface expansion, cortical thickness increase, reduction in cortical anisotropy and increase in neurite orientation dispersion. By term-equivalent age, preterm infants had on average increased cortical tissue water content and reduced neurite density index in the posterior parts of the cortex, and greater cortical thickness anteriorly compared to term-born infants. While individual preterm infants were more likely to show extreme deviations (over 3.1 standard deviations) from normative cortical maturation compared to term-born infants, these extreme deviations were highly variable and showed very little spatial overlap between individuals. Measures of regional cortical development were associated with age at birth, but not with neurodevelopment at 18 months. ConclusionWe showed that preterm birth alters cortical micro and macrostructural maturation near the time of fullterm birth. Deviations from normative development were highly variable between individual preterm infants.

neuroscience↗

Multi-channel 4D parametrized Atlas of Macro- and Microstructural Neonatal Brain Development

Structural and diffusion MRI provide complimentary anatomical and microstructural characterization of early brain maturation. The existing models of the developing brain in time include only either structural or diffusion channels. Furthermore, there is a lack of tools for combined analysis of structural and diffusion MRI in the same reference space. In this work we propose methodology to generate multi-channel (MC) continuous spatio-temporal parametrized atlas of brain development based on MC registration driven by both T2-weighted and orientation distribution functions (ODF) channels along with the Gompertz model (GM) fitting of the signals and spatial transformations in time. We construct a 4D MC atlas of neonatal brain development during 38 to 44 week PMA range from 170 normal term subjects from developing Human Connectomme Project. The resulting atlas consists of fourteen spatio-temporal microstructural indices and two parcellation maps delineating white matter tracts and neonatal transient structures. We demonstrate applicability of the atlas for quantitative region-specific comparison of 140 term and 40 preterm subjects scanned at the term-equivalent age. We show multi-parametric microstructural differences in multiple white matter regions, including the transient compartments. The atlas and software will be available after publication of the article.

neuroscience↗

dStripe: slice artefact correction in diffusion MRI via constrained neural network

MRI scanner and sequence imperfections and advances in reconstruction and imaging techniques to increase motion robustness can lead to inter-slice intensity variations in Echo Planar Imaging. Leveraging deep convolutional neural networks as universal image filters, we present a data-driven method for the correction of acquisition artefacts that manifest as inter-slice inconsistencies, regardless of their origin. This technique can be applied to motion- and dropout-artefacted data by embedding it in a reconstruction pipeline. The network is trained in the absence of ground-truth data on, and finally applied to, the reconstructed multi-shell high angular resolution diffusion imaging signal to produce a corrective slice intensity modulation field. This correction can be performed in either motion-corrected or scattered source-space. We focus on gaining control over the learned filter and the image data consistency via built-in spatial frequency and intensity constraints. The end product is a corrected image reconstructed from the original raw data, modulated by a multiplicative field that can be inspected and verified to match the expected features of the artefact. In-plane, the correction approximately preserves the contrast of the diffusion signal and throughout the image series, it reduces interslice inconsistencies within and across subjects without biasing the data. We apply our pipeline to enhance the super-resolution reconstruction of neonatal multi-shell high angular resolution data as acquired in the developing Human Connectome Project.

neuroscience↗

Predicting age and clinical risk from the neonatal connectome

The development of perinatal brain connectivity underpins motor, cognitive and behavioural abilities in later life. Diffusion MRI allows the characterisation of subtle inter-individual differences in structural brain connectivity. Individual brain connectivity maps (connectomes) are by nature high in dimensionality and are complex to interpret. Machine learning methods are a powerful tool to uncover properties of the connectome which are not readily visible, and can give us clues as to how and why individual developmental trajectories differ. In this manuscript we used Deep Neural Networks and Random Forests to predict demographic and neurodevelopmental characteristics from neonatal structural connectomes in a large sample of babies (n = 524) from the developing Human Connectome Project. We achieved an accurate prediction of post menstrual age (PMA) at scan in term-born infants (Mean absolute error (MAE) = 0.72 weeks, r = 0.83 and p<0.001). We also achieved good accuracy when predicting gestational age at birth in a cohort of term and preterm babies scanned at term equivalent age (MAE = 2.21 weeks, r = 0.82, p<0.001). We subsequently used sensitivity analysis to obtain feature relevance from our prediction models, with the most important connections for prediction of PMA and GA found to be predominantly thalamocortical. From our models of PMA at scan for infants born at term, we computed a brain maturation index (predicted age minus actual age) of individual preterm neonates and found a significant correlation between this index and motor outcome at 18 months corrected age. Our results demonstrate the applicability of machine learning techniques in analyses of the neonatal connectome, and suggest that a neural substrate for later developmental outcome is detectable at term equivalent age.

neuroscience↗

A data-driven approach to optimising the encoding for multi-shell diffusion MRI with application to neonatal imaging

Diffusion MRI has the potential to provide important information about the connectivity and microstructure of the human brain during normal and abnormal development, non-invasively and in vivo. Recent developments in MRI hardware and reconstruction methods now permit the acquisition of large amounts of data within relatively short scan times. This makes it possible to acquire more informative multi-shell data, with diffusion-sensitisation applied along many directions over multiple b-value shells. Such schemes are characterised by the number of shells acquired, and the specific b-value and number of directions sampled for each shell. However, there is currently no clear consensus as to how to optimise these parameters. In this work, we propose a means of optimising multi-shell acquisition schemes by estimating the information content of the diffusion MRI signal, and optimising the acquisition parameters for sensitivity to the observed effects, in a manner agnostic to any particular diffusion analysis method that might subsequently be applied to the data. This method was used to design the acquisition scheme for the neonatal diffusion MRI sequence used in the developing Human Connectome Project, which aims to acquire high quality data and make it freely available to the research community. The final protocol selected by the algorithm, and currently in use within the dHCP, consists of b = 0, 400, 1000, 2600 s/mm2 with 20, 64, 88 & 128 DW directions per shell respectively.\n\nHighlightsO_LIA data driven method is presented to design multi-shell diffusion MRI acquisition schemes (b-values and no. directions).\nC_LIO_LIThis method optimises the multi-shell scheme for maximum sensitivity to the information content in the signal.\nC_LIO_LIWhen applied in neonates, the data suggest that a b=0 + 3 shell strategy is appropriate\nC_LI

neuroscience↗

Fetal whole-heart 4D flow cine MRI using multiple non-coplanar balanced SSFP stacks

PurposeTo develop an MRI framework for reconstruction of 4D velocity vector blood flow volumes for visualisation and quantification of circulation in the fetal heart and major vessels.\n\nMethodsA novel method of velocity-encoding using multiple non-coplanar stacks of bSSFP phase images was combined with a previous framework for reconstruction of motion-corrected 4D magnitude cine volumes to generate spatiotemporally-paired 4D flow cine volumes of the fetal circulatory system. The multiple stack velocity-encoding scheme was validated in a simulated flow phantom and compared with a gold-standard method for velocity-encoding in a physical flow phantom. The 4D flow cine framework was evaluated in seven fetal subjects. Reconstructed 4D flow volumes were evaluated by an expert fetal cardiologist and preliminary flow measurements were taken in various major vessels of the heart.\n\nResultsPhantom experiments showed that the multiple non-coplanar stack velocity-encoding scheme was accurate. The 4D flow cine reconstruction framework was robust in fetal subjects and generated multi-dimensional velocity vector maps of blood flow through the cardiac cycle. Directionality of blood flow was consistent with expected fetal circulatory hemodynamics. Relative blood flow rates in the major vessels were in line with previous observations, although absolute values were underestimated by a factor of approximately two due to limitations of spatial and temporal resolution.\n\nConclusion4D flow cine volumes can be reconstructed from multiple non-coplanar stacks of slices. The proposed framework was used to visualise and quantify flow through the whole fetal heart and great vessels, but is applicable to any imaging scenario where motion is a major challenge.

bioengineering↗

MRtrix3: A fast, flexible and open software framework for medical image processing and visualisation

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 development of new applications, whilst retaining high computational performance and a consistent command-line interface between applications. In this article, we provide a high-level overview of the features of the MRtrix3 framework and general-purpose image processing applications provided with the software.

neuroscience↗

Grey matter biomarker identification in Schizophrenia: detecting regional alterations and their underlying substrates

State-of-the-art approaches in Schizophrenia research investigate neuroanatomical biomarkers using structural Magnetic Resonance Imaging. However, current models are 1) voxel-wise, 2) difficult to interpret in biologically meaningful ways, and 3) difficult to replicate across studies. Here, we propose a machine learning framework that enables the identification of sparse, region-wise grey matter neuroanatomical biomarkers and their underlying biological substrates by integrating well-established statistical and machine learning approaches. We address the computational issues associated with application of machine learning on structural MRI data in Schizophrenia, as discussed in recent reviews, while promoting transparent science using widely available data and software. In this work, a cohort of patients with Schizophrenia and healthy controls was used. It was found that the cortical thickness in left pars orbitalis seems to be the most reliable measure for distinguishing patients with Schizophrenia from healthy controls.\n\nHighlightsO_LIWe present a sparse machine learning framework to identify biologically meaningful neuroanatomical biomarkers for Schizophrenia\nC_LIO_LIOur framework addresses methodological pitfalls associated with application of machine learning on structural MRI data in Schizophrenia raised by several recent reviews\nC_LIO_LIOur pipeline is easy to replicate using widely available software packages\nC_LIO_LIThe presented framework is geared towards identification of specific changes in brain regions that relate directly to the pathology rather than classification per se\nC_LI

neuroscience↗

Higher order spherical harmonics reconstruction of fetal diffusion MRI with intensity correction

We present a comprehensive method for reconstruction of fetal diffusion MRI signal using a higher order spherical harmonics representation, that includes motion, distortion and intensity correction. By applying constrained spherical deconvolution and whole brain tractography to reconstructed fetal diffusion MRI we are able to identify main WM tracts and anatomically plausible fiber crossings. The proposed methodology facilitates detailed investigation of developing brain connectivity and microstructure in-utero.

neuroscience↗

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.

neuroscience↗