Vascular-water-exchange MRI (VEXI) enables the detection of subtle AXR alterations in Alzheimer's disease without MRI contrast agent, which may relate to BBB integrity

Blood-brain barrier (BBB) impairment is an important pathophysiological process in Alzheimer's 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 proposed 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 the apparent water exchange across the BBB (AXRBBB) measured by VEXI shows higher values in MCI compared with NC, and this higher AXRBBB happens specifically in the hippocampus. This increase in AXRBBB value gets larger and extends to more brain regions (medial orbital frontal cortex and thalamus) from MCI group to the AD group. Furthermore, we find that the AXRBBB values of these three regions is correlated significantly with the 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.

Automated summary

Blood-brain barrier (BBB) impairment is a key factor in Alzheimer's disease (AD) and can be used as a biomarker for early diagnosis. However, current neuroimaging methods require contrast agents, limiting their use in a large population. This study tested the feasibility of using vascular water exchange MRI (VEXI), a contrast agent-free method, to detect BBB breakdown in AD. The results showed that the apparent water exchange across the BBB measured by VEXI was higher in mild cognitive impairment (MCI) patients compared to normal cognition subjects, particularly in the hippocampus. The increase in water exchange extended to more brain regions in AD patients, and these changes were correlated with cognitive impairment.