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      Optimising neonatal fMRI data analysis: Design and validation of an extended dHCP preprocessing pipeline to characterise noxious-evoked brain activity in infants

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          Abstract

          The infant brain is unlike the adult brain, with considerable differences in morphological, neurodynamic, and haemodynamic features. As the majority of current MRI analysis tools were designed for use in adults, a primary objective of the Developing Human Connectome Project (dHCP) is to develop optimised methodological pipelines for the analysis of neonatal structural, resting state, and diffusion MRI data. Here, in an independent neonatal dataset we have extended and optimised the dHCP fMRI preprocessing pipeline for the analysis of stimulus-response fMRI data. We describe and validate this extended dHCP fMRI preprocessing pipeline to analyse changes in brain activity evoked following an acute noxious stimulus applied to the infant's foot. We compare the results obtained from this extended dHCP pipeline to results obtained from a typical FSL FEAT-based analysis pipeline, evaluating the pipelines' outputs using a wide range of tests. We demonstrate that a substantial increase in spatial specificity and sensitivity to signal can be attained with a bespoke neonatal preprocessing pipeline through optimised motion and distortion correction, ICA-based denoising, and haemodynamic modelling. The improved sensitivity and specificity, made possible with this extended dHCP pipeline, will be paramount in making further progress in our understanding of the development of sensory processing in the infant brain.

          Highlights

          • The dHCP fMRI preprocessing pipeline is generalizable to stimulus-evoked datasets.

          • Customised FIX denoising in infant fMRI data substantially improves data quality.

          • The dHCP pipeline greatly improves spatial specificity and sensitivity to signal.

          • Bespoke fMRI data analysis outperforms typical analytical methods for neonatal data.

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          Most cited references33

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          Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration.

          All fields of neuroscience that employ brain imaging need to communicate their results with reference to anatomical regions. In particular, comparative morphometry and group analysis of functional and physiological data require coregistration of brains to establish correspondences across brain structures. It is well established that linear registration of one brain to another is inadequate for aligning brain structures, so numerous algorithms have emerged to nonlinearly register brains to one another. This study is the largest evaluation of nonlinear deformation algorithms applied to brain image registration ever conducted. Fourteen algorithms from laboratories around the world are evaluated using 8 different error measures. More than 45,000 registrations between 80 manually labeled brains were performed by algorithms including: AIR, ANIMAL, ART, Diffeomorphic Demons, FNIRT, IRTK, JRD-fluid, ROMEO, SICLE, SyN, and four different SPM5 algorithms ("SPM2-type" and regular Normalization, Unified Segmentation, and the DARTEL Toolbox). All of these registrations were preceded by linear registration between the same image pairs using FLIRT. One of the most significant findings of this study is that the relative performances of the registration methods under comparison appear to be little affected by the choice of subject population, labeling protocol, and type of overlap measure. This is important because it suggests that the findings are generalizable to new subject populations that are labeled or evaluated using different labeling protocols. Furthermore, we ranked the 14 methods according to three completely independent analyses (permutation tests, one-way ANOVA tests, and indifference-zone ranking) and derived three almost identical top rankings of the methods. ART, SyN, IRTK, and SPM's DARTEL Toolbox gave the best results according to overlap and distance measures, with ART and SyN delivering the most consistently high accuracy across subjects and label sets. Updates will be published on the http://www.mindboggle.info/papers/ website.
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            Multiband multislice GE-EPI at 7 tesla, with 16-fold acceleration using partial parallel imaging with application to high spatial and temporal whole-brain fMRI.

            Parallel imaging in the form of multiband radiofrequency excitation, together with reduced k-space coverage in the phase-encode direction, was applied to human gradient echo functional MRI at 7 T for increased volumetric coverage and concurrent high spatial and temporal resolution. Echo planar imaging with simultaneous acquisition of four coronal slices separated by 44mm and simultaneous 4-fold phase-encoding undersampling, resulting in 16-fold acceleration and up to 16-fold maximal aliasing, was investigated. Task/stimulus-induced signal changes and temporal signal behavior under basal conditions were comparable for multiband and standard single-band excitation and longer pulse repetition times. Robust, whole-brain functional mapping at 7 T, with 2 x 2 x 2mm(3) (pulse repetition time 1.25 sec) and 1 x 1 x 2mm(3) (pulse repetition time 1.5 sec) resolutions, covering fields of view of 256 x 256 x 176 mm(3) and 192 x 172 x 176 mm(3), respectively, was demonstrated with current gradient performance. (c) 2010 Wiley-Liss, Inc.
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              Incorporating outlier detection and replacement into a non-parametric framework for movement and distortion correction of diffusion MR images

              Despite its great potential in studying brain anatomy and structure, diffusion magnetic resonance imaging (dMRI) is marred by artefacts more than any other commonly used MRI technique. In this paper we present a non-parametric framework for detecting and correcting dMRI outliers (signal loss) caused by subject motion. Signal loss (dropout) affecting a whole slice, or a large connected region of a slice, is frequently observed in diffusion weighted images, leading to a set of unusable measurements. This is caused by bulk (subject or physiological) motion during the diffusion encoding part of the imaging sequence. We suggest a method to detect slices affected by signal loss and replace them by a non-parametric prediction, in order to minimise their impact on subsequent analysis. The outlier detection and replacement, as well as correction of other dMRI distortions (susceptibility-induced distortions, eddy currents (EC) and subject motion) are performed within a single framework, allowing the use of an integrated approach for distortion correction. Highly realistic simulations have been used to evaluate the method with respect to its ability to detect outliers (types 1 and 2 errors), the impact of outliers on retrospective correction of movement and distortion and the impact on estimation of commonly used diffusion tensor metrics, such as fractional anisotropy (FA) and mean diffusivity (MD). Data from a large imaging project studying older adults (the Whitehall Imaging sub-study) was used to demonstrate the utility of the method when applied to datasets with severe subject movement. The results indicate high sensitivity and specificity for detecting outliers and that their deleterious effects on FA and MD can be almost completely corrected.
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                Author and article information

                Contributors
                Journal
                Neuroimage
                Neuroimage
                Neuroimage
                Academic Press
                1053-8119
                1095-9572
                01 February 2019
                01 February 2019
                : 186
                : 286-300
                Affiliations
                [a ]Department of Paediatrics, University of Oxford, Oxford, United Kingdom
                [b ]FMRIB, Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, United Kingdom
                Author notes
                []Corresponding author. Department of Paediatrics, Level 2 Children's Hospital, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom. rebeccah.slater@ 123456paediatrics.ox.ac.uk
                [1]

                Equal contribution.

                [2]

                Equal contribution.

                Article
                S1053-8119(18)32076-7
                10.1016/j.neuroimage.2018.11.006
                6347570
                30414984
                e2dbebc7-f2f4-43fa-ac7a-7d1c153a66cd
                © 2018 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 13 July 2018
                : 16 October 2018
                : 6 November 2018
                Categories
                Article

                Neurosciences
                developing human connectome project,functional magnetic resonance imaging,preprocessing,haemodynamic response function,neonate,pain

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