Test-retest reliability of cerebral blood flow in healthy individuals using arterial spin labeling: Findings from the EMBARC study

Abstract

Introduction: Previous investigations of test-retest reliability of cerebral blood flow (CBF) at rest measured with pseudo-continuous Arterial Spin Labeling (pCASL) demonstrated good reliability, but are limited by the use of similar scanner platforms. In the present study we examined test-retest reliability of CBF in regions implicated in emotion and the default mode network.

Material and methods: We measured absolute and relative CBF at rest in thirty-one healthy subjects in two scan sessions, one week apart, at four different sites and three different scan platforms. We derived CBF from pCASL images with an automated algorithm and calculated intra-class correlation coefficients (ICCs) across sessions for regions of interest. In addition, we investigated site effects.

Results: For both absolute and relative CBF measures, ICCs were good to excellent (i.e. >0.6) in most brain regions, with highest values observed for the subgenual anterior cingulate cortex and ventral striatum. A leave-one-site-out cross validation analysis did not show a significant effect for site on whole brain CBF and there was no proportional bias across sites. However, a significant site effect was present in the repeated measures ANOVA.

Conclusions: The high test-retest reliability of CBF measured with pCASL in a range of brain regions implicated in emotion and salience processing, emotion regulation, and the default mode network, which have been previously linked to depression symptomatology supports its use in studies that aim to identify neuroimaging biomarkers of treatment response.

Keywords: Arterial spin labeling; Cerebral blood flow; Reliability; fMRI.

Fig. 1

Bland-Altman plot of repeated CBF measurements (baseline and week 1) across four sites in absolute whole-brain gray matter CBF (mL/100 g/min). The Bland-Altman plot represents intrascan aCBF differences plotted against mean aCBF. Intrascan aCBF differences are randomly distributed and are not dependent on mean aCBF. Multiple linear regression demonstrated no similarity difference between sites. The solid middle line denotes the bias from zero, which represents absolute no difference between baseline and week 1 measures. The dotted top and bottom lines represents limits of agreement (i.e. bias ± 1.96 × standard deviation). Different colors and symbols represent each of the four sites. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Bar graph representing mean absolute whole-brain gray matter CBF (mL/100 g/min) at baseline and week 1 for each site. Each cluster represents a specific site. Each bar constitutes either baseline (diagonal lines) or week 1 (horizontal lines) mean whole-brain gray matter aCBF. Asterisks denote a significant difference (p < 0.05) between sites resulting from a mean effect of site in the repeated measures ANOVA.