Abstract

BackgroundLarge-scale longitudinal and multi-centre studies are used to explore neuroimaging markers of normal ageing, and neurodegenerative and mental health disorders. Longitudinal changes in brain structure are typically small, therefore the reliability of automated techniques is crucial. Determining the effects of different factors on reliability allows investigators to control those adversely affecting reliability, calculate statistical power, or even avoid particular brain measures with low reliability. This study examined the impact of several image acquisition and processing factors and documented the test-retest reliability of structural MRI measurements. MethodsIn Phase I, 20 healthy adults (11 females; aged 20–30 years) were scanned on two occasions three weeks apart on the same scanner using the ADNI-3 protocol. On each occasion, individuals were scanned twice (repetition), after re-entering the scanner (reposition) and after tilting their head forward. At one year follow-up, nine returning individuals and 11 new volunteers were recruited for Phase II (11 females; aged 22–31 years). Scans were acquired on two different scanners using the ADNI-2 and ADNI-3 protocols. Structural images were processed using FreeSurfer (v5.3.0, 6.0.0 and 7.1.0) to provide subcortical and cortical volume, cortical surface area and thickness measurements. Intra-class correlation coefficients (ICC) were calculated to estimate test-retest reliability. We examined the effect of repetition, reposition, head tilt, time between scans, MRI sequence and scanner on reliability of structural brain measurements. Mean percentage differences were also calculated in supplementary analyses. ResultsUsing the FreeSurfer v7.1.0 longitudinal pipeline, we observed high reliability for subcortical and cortical volumes, and cortical surface areas at repetition, reposition, three weeks and one year (mean ICCs>0.97). Cortical thickness reliability was lower (mean ICCs>0.82). Head tilt had the greatest adverse impact on ICC estimates, for example reducing mean right cortical thickness to ICC=0.74. In contrast, changes in ADNI sequence or MRI scanner had a minimal effect. We observed an increase in reliability for updated FreeSurfer versions, with the longitudinal pipeline consistently having a higher reliability than the cross-sectional pipeline. DiscussionLongitudinal studies should monitor or control head tilt to maximise reliability. We provided the ICC estimates and mean percentage differences for all FreeSurfer brain regions, which may inform power analyses for clinical studies and have implications for the design of future longitudinal studies.

Highlights

  • Longitudinal and multi-centre studies have become increasingly popular to explore neuroimaging markers of normal ageing, and neurodegenerative and mental health disorders (Misra et al, 2009; Scahill et al., NeuroImage 246 (2022) 118751 brain volume studies, such as UK Biobank (Elliott et al, 2018), ENIGMA Consortium (Thompson et al, 2014) and Lifebrain (Walhovd et al, 2018)

  • Demographic and structural MRI data for a subset of 24 participants is publicly available to download at https://sites.google.com/view/pinstudy

  • Head tilt had a greater adverse impact on reliability of brain measurements compared to participant repositioning and changes in MRI sequence or scanner

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Summary

Introduction

Longitudinal and multi-centre studies have become increasingly popular to explore neuroimaging markers of normal ageing, and neurodegenerative and mental health disorders (Misra et al, 2009; Scahill et al., NeuroImage 246 (2022) 118751 brain volume studies, such as UK Biobank (Elliott et al, 2018), ENIGMA Consortium (Thompson et al, 2014) and Lifebrain (Walhovd et al, 2018). It is imperative to quantify and report the reliability of all segmented brain regions, as well as examining the effects of a range of image acquisition and processing factors on reliability This will allow future studies to address factors that may reduce the reliability of MRI-derived measurements and so increase sensitivity of longitudinal MRI to real changes of interest. We examined the effect of repetition, reposition, head tilt, time between scans, MRI sequence and scanner on reliability of structural brain measurements. We provided the ICC estimates and mean percentage differences for all FreeSurfer brain regions, which may inform power analyses for clinical studies and have implications for the design of future longitudinal studies

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