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Diffusion tensor image segmentation of the cerebrum provides a single measure of cerebral small vessel disease severity related to cognitive change.

Williams, OA; Zeestraten, EA; Benjamin, P; Lambert, C; Lawrence, AJ; Mackinnon, AD; Morris, RG; Markus, HS; Charlton, RA; Barrick, TR (2017) Diffusion tensor image segmentation of the cerebrum provides a single measure of cerebral small vessel disease severity related to cognitive change. Neuroimage Clin, 16. pp. 330-342. ISSN 2213-1582 https://doi.org/10.1016/j.nicl.2017.08.016
SGUL Authors: Barrick, Thomas Richard

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Abstract

Cerebral small vessel disease (SVD) is the primary cause of vascular cognitive impairment and is associated with decline in executive function (EF) and information processing speed (IPS). Imaging biomarkers are needed that can monitor and identify individuals at risk of severe cognitive decline. Recently there has been interest in combining several magnetic resonance imaging (MRI) markers of SVD into a unitary score to describe disease severity. Here we apply a diffusion tensor image (DTI) segmentation technique (DSEG) to describe SVD related changes in a single unitary score across the whole cerebrum, to investigate its relationship with cognitive change over a three-year period. 98 patients (aged 43-89) with SVD underwent annual MRI scanning and cognitive testing for up to three years. DSEG provides a vector of 16 discrete segments describing brain microstructure of healthy and/or damaged tissue. By calculating the scalar product of each DSEG vector in reference to that of a healthy ageing control we generate an angular measure (DSEG θ) describing the patients' brain tissue microstructural similarity to a disease free model of a healthy ageing brain. Conventional MRI markers of SVD brain change were also assessed including white matter hyperintensities, cerebral atrophy, incident lacunes, cerebral-microbleeds, and white matter microstructural damage measured by DTI histogram parameters. The impact of brain change on cognition was explored using linear mixed-effects models. Post-hoc sample size analysis was used to assess the viability of DSEG θ as a tool for clinical trials. Changes in brain structure described by DSEG θ were related to change in EF and IPS (p < 0.001) and remained significant in multivariate models including other MRI markers of SVD as well as age, gender and premorbid IQ. Of the conventional markers, presence of new lacunes was the only marker to remain a significant predictor of change in EF and IPS in the multivariate models (p = 0.002). Change in DSEG θ was also related to change in all other MRI markers (p < 0.017), suggesting it may be used as a surrogate marker of SVD damage across the cerebrum. Sample size estimates indicated that fewer patients would be required to detect treatment effects using DSEG θ compared to conventional MRI and DTI markers of SVD severity. DSEG θ is a powerful tool for characterising subtle brain change in SVD that has a negative impact on cognition and remains a significant predictor of cognitive change when other MRI markers of brain change are accounted for. DSEG provides an automatic segmentation of the whole cerebrum that is sensitive to a range of SVD related structural changes and successfully predicts cognitive change. Power analysis shows DSEG θ has potential as a monitoring tool in clinical trials. As such it may provide a marker of SVD severity from a single imaging modality (i.e. DTIs).

Item Type: Article
Additional Information: © 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/). Correction available at https://doi.org/10.1016/j.nicl.2019.101742
Keywords: Biomarker, Cerebral small vessel disease, Cognitive decline, DSEG, diffusion tensor image segmentation algorithm, Diffusion segmentation, Diffusion tensor imaging, EF, executive functions, IPS, information processing speed, SVD, cerebral small vessel disease
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Neuroscience (INCCNS)
Journal or Publication Title: Neuroimage Clin
ISSN: 2213-1582
Language: eng
Dates:
DateEvent
2017Published
15 August 2017Published Online
12 August 2017Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
081589Wellcome Trusthttp://dx.doi.org/10.13039/100004440
374Research into AgeingUNSPECIFIED
PubMed ID: 28861335
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109116
Publisher's version: https://doi.org/10.1016/j.nicl.2017.08.016

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