DOI: 10.1002/alz.081793 ISSN: 1552-5260

Blood‐brain barrier permeability measured with arterial spin labeling as potential cerebrovascular biomarker over the lifespan

Beatriz E. Padrela, Mervin Tee, Sneve H Markus, Oliver Geier, Amnah Mahroo, Håkon Grydeland, Tormod Fladby, Klaus Eickel, Matthias Günther, Frederik Barkhof, Saima Hilal, Henk‐Jan Mutsaerts, Jan Petr
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Blood‐brain barrier (BBB) dysfunction is considered a hallmark of Alzheimer’s disease (AD), making non‐invasive imaging of BBB with arterial spin labeling (ASL) MRI a potential imaging biomarker (BBB‐ASL). However, the normal BBB development over the lifespan is unknown. Here, we created population‐based BBB‐ASL permeability reference maps, and aimed to investigate associations between BBB‐ASL, chronological age, and biological cerebrovascular age – expressed as white matter hyperintensities (WMH) volume.


Cognitively‐unimpaired (CU) participants were included from Center for Lifespan Changes in Brain and Cognition (LCBC) (n = 28, age 58.9±16.1y) and University of Singapore (n = 30, age 55.8±6.1y). The Singapore cohort is known to be vascularly compromised and thus expected to have early cerebrovascular pathology in the form of WMH. Multi‐echo, multi‐post‐labeling‐delay pseudo‐continuous ASL images were acquired at two identical Siemens 3T scanners and analyzed with ExploreASL. Gray matter (GM) BBB water time‐of‐exchange (Tex) was quantified with and without partial‐volume correction (PVC). For Singapore data, WMH were segmented on 3D FLAIR. Linear regression models were used to investigate associations of Tex with age and WMH volume, with and without covarying for sex and site.


Both site population‐averages (Figure 1) show similar Tex patterns, with slightly higher posterior variability in the Singapore data. GM Tex was negatively associated with age (Figure 2A) irrespective of PVC, and after covarying for sex and site (Table 1). GM Tex was also negatively associated with WMH volume (ß = ‐0.005, p = 0.012), although the association became non‐significant if both PVC and sex and site corrections were applied (ß = ‐0.005, p = 0.068).


Our findings support the hypothesis of increased BBB permeability with aging and there are signs of association with increased cerebrovascular age assessed with WMH volume. We aim to further increase our sample size and also investigate associations with other AD biomarkers.

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