Vascular-water-exchange MRI (VEXI) enables the detection of subtle BBB breakdown in Alzheimer's disease without MRI contrast agent

Blood-brain barrier (BBB) impairment is an important pathophysiological process in Alzheimers disease (AD) and a potential biomarker for early diagnosis of AD. However, most current neuroimaging methods assessing BBB function need the injection of exogenous contrast agents (or tracers), which limits the application of these methods in a large population. In this study, we aim to explore the feasibility of vascular water exchange MRI (VEXI), a diffusion-MRI-based method to assess the BBB permeability to water molecules without using a contrast agent, in the detection of the BBB breakdown in AD. We tested VEXI on a 3T MRI scanner on three groups: AD patients (AD group), mild cognitive impairment (MCI) patients due to AD (MCI group), and the age-matched normal cognition subjects (NC group). Interestingly, we find that VEXI can detect the BBB permeability to water molecules increase in MCI and this BBB breakdown happens specifically in the hippocampus. This BBB breakdown gets worse and extends to more brain regions (orbital frontal cortex and thalamus) from MCI group to the AD group. Furthermore, we find that the BBB breakdown of these three regions detected by VEXI is correlated significantly with impairment of respective cognitive domains independent of age, sex and education. These results suggest VEXI is a promising method to assess the BBB breakdown in AD. HighlightsO_LIThe vascular water exchange MRI (VEXI) is a contrast-agent-free method to assess BBB permeability C_LIO_LIBBB breakdown happens specifically in the hippocampus, orbital frontal cortex, and thalamus in AD C_LIO_LIBBB breakdown detected by VEXI is significantly correlated with cognitive dysfunction C_LI