Test–retest reliability of arterial spin labelling for cerebral blood flow in older adults with small vessel disease

Lauren R Binnie ,Usman Khan,Mathilde Pauls ,Brian Clarke,Thomas R Barrick,Rebecca J Williams ,Sarah Trippier,Rita Ghatala,Egill Rostrup,Jeremy Madigan ,Shai Betteridge,Fearghal A.h Hainsworth ,Barry Moynihan,Franklyn A Howe,Christina Kruuse,Philip Benjamin,Anan Shtaya ,Jeremy D Isaacs ,Anthony Pereira ,Mohani‐Preet K Dhillon ,Bhavini Patel,Catherine A Spilling,Atticus H Hainsworth

doi:10.1007/s12975-021-00983-5

Abstract

Cerebral small vessel disease (SVD) is common in older people and is associated with lacunar stroke, white matter hyperintensities (WMH) and vascular cognitive impairment. Cerebral blood flow (CBF) is reduced in SVD, particularly within white matter.Here we quantified test–retest reliability in CBF measurements using pseudo-continuous arterial spin labelling (pCASL) in older adults with clinical and radiological evidence of SVD (N=54, mean (SD): 66.9 (8.7) years, 15 females/39 males). We generated whole-brain CBF maps on two visits at least 7 days apart (mean (SD): 20 (19), range 7-117 days).Test–retest reliability for CBF was high in all tissue types, with intra-class correlation coefficient [95%CI]: 0.758 [0.616, 0.852] for whole brain, 0.842 [0.743, 0.905] for total grey matter, 0.771 [0.636, 0.861] for deep grey matter (caudate-putamen and thalamus), 0.872 [0.790, 0.923] for normal-appearing white matter (NAWM) and 0.780 [0.650, 0.866] for WMH (all p<0.001). ANCOVA models indicated significant decline in CBF in total grey matter, deep grey matter and NAWM with increasing age and diastolic blood pressure (all p<0.001). CBF was lower in males relative to females (p=0.013 for total grey matter, p=0.004 for NAWM).We conclude that pCASL has high test–retest reliability as a quantitative measure of CBF in older adults with SVD. These findings support the use of pCASL in routine clinical imaging and as a clinical trial endpoint.All data come from the PASTIS trial, prospectively registered at: https://eudract.ema.europa.eu (2015-001235-20, registered 13/05/2015), http://www.clinicaltrials.gov (NCT02450253, registered 21/05/2015).

Highlights

MethodsCerebral small vessel disease (SVD) is common in older people, observed radiologically as focal lacunar infarcts, micro-haemorrhages and diffuse white matter hyperintensities (WMH) on T2-weighted MRI scans [1, 2]
We report whole-brain cerebral blood flow (CBF) maps measured by pseudo-continuous arterial spin labelling [15, 16] in a wellcharacterised cohort of older adults with symptomatic SVD [17]
For each participant CBF data were documented for visit 1 and visit 2 in whole brain and in four tissue types: grey matter, deep grey matter (DGM), normal-appearing white matter (NAWM) and WMH

Summary

Introduction

Cerebral small vessel disease (SVD) is common in older people, observed radiologically as focal lacunar infarcts, micro-haemorrhages and diffuse white matter hyperintensities (WMH) on T2-weighted MRI scans [1, 2]. As the test–retest reproducibility of this method has not been quantified in people with SVD, it has not entered routine use for clinical assessment or as a clinical trial outcome measure. We report whole-brain CBF maps measured by pseudo-continuous arterial spin labelling (pCASL) [15, 16] in a wellcharacterised cohort of older adults with symptomatic SVD [17]. We aimed to test whether pCASL is an effective method for quantitative assessment of CBF in people with SVD, in white matter areas where absolute CBF values are low [7, 10, 18]. We aimed to quantify test–retest reliability in CBF measured by pCASL within this participant group, using CBF maps derived from two successive visits, at least 7 days apart

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Conclusion