Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury

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Title: Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury
Authors: Cole, JH
Jolly, A
De Simoni, S
Bourke, N
Patel, M
Scott, G
Sharp, D
Item Type: Journal Article
Abstract: Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of magnetic resonance imaging. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions, and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 moderate/severe traumatic brain injury patients (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (one-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterised using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarised regionally and compared with clinical and neuropsychological measures. Traumatic brain injury patients showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over one year was pronounced following traumatic brain injury. Traumatic brain injury patients lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the follow-up period, as well as to changes in memory performance, prior to multiple comparison correction. In conclusion, traumatic brain injury results in progressive loss of brain tissue volume, which continues for many years post-injury. Atrophy is most prominent in the white matter, but is also more pronounced in cortical sulci compared to gyri. These findings suggest the Jacobian determinant provides a method of quantifying brain atrophy following a traumatic brain injury and is informative in determining the long-term neurodegenerative effects after injury. Power calculations indicate that Jacobian determinant images are an efficient surrogate marker in clinical trials of neuroprotective therapeutics.
Issue Date: 4-Jan-2018
Date of Acceptance: 8-Nov-2017
ISSN: 1460-2156
Publisher: Oxford University Press (OUP)
Start Page: 822
End Page: 836
Journal / Book Title: Brain
Volume: 141
Issue: 3
Copyright Statement: © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Royal College Of Surgeons Of England
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: NIHR-RP-011-048
RDC04 79560
Keywords: brain atrophy
traumatic brain injury
voxel-based morphometry
11 Medical And Health Sciences
17 Psychology And Cognitive Sciences
Neurology & Neurosurgery
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine

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