New physiological insights using multi-TE ASL MRI measuring blood-brain barrier water exchange after caffeine intake

Caffeine, a known neurostimulant and adenosine antagonist, affects brain physiology by decreasing cerebral blood flow. It interacts with adenosine receptors to induce vasoconstriction, potentially disrupting brain homeostasis. However, the impact of caffeine on blood-brain barrier (BBB) permeability to water remains underexplored. This study investigated the water exchange via the BBB in a perturbed physiological condition caused by caffeine ingestion, using the multiple echo time (multi-TE) arterial spin labeling (ASL) technique.

Ten healthy, regular coffee drinkers (age = 31 ± 9 years, 3 females) were scanned to acquire five measurements before and six measurements after caffeine ingestion. Data were analyzed with a multi-TE two-compartment model to estimate exchange time (Tex), serving as a proxy for BBB permeability to water. Additionally, cerebral blood flow (CBF), arterial transit time (ATT), and intravoxel transit time (ITT) were investigated.

Following caffeine intake, mean gray matter CBF showed a significant time-dependent decrease (P < 0.01). In contrast, Tex, ATT, and ITT did not exhibit significant time-dependent change. However, a non-significant decreasing trend was observed for Tex and ITT, respectively, while ATT showed an increasing trend over time.

The observed decreasing trend in Tex after caffeine ingestion suggests a potential increase in water flux across the BBB, which may represent a compensatory mechanism to maintain brain homeostasis in response to the caffeine-induced reduction in CBF. Further studies with larger sample sizes are needed to validate and expand upon these findings.