Diffusion-weighted arterial spin labeling MRI to investigate mannitol-induced blood brain barrier disruption

Purpose: Diffusion-weighted arterial spin labeling (DW-ASL) MRI has been proposed to determine the rate of water exchange (K_w) across the blood brain barrier (BBB). This study aims to further evaluate K_w MRI by comparing it with standard dynamic contrast-enhanced (DCE) MRI and histology in association with mannitol-induced disruption of the BBB. Methods: DW-ASL was measured using a multiple b-value MRI protocol in normal rats at three post-labeling delays (N = 19), before and after intra-carotid injection of mannitol to disrupt BBB in one hemisphere (N = 13). An approach using only two b-values to detect mannitol-induced changes was also tested. DCE MRI and Evans blue histology were performed on the same animals. Quantitative analysis and pixel-by-pixel correlation were performed amongst K_w, DCE MRI and Evans blue histology. Results: K_w in the grey matter in the normal rat brain was 252 ± 38 min⁻¹ (±standard error of the mean). The two b-value approach provided reasonable approximation of multiple-b DW-ASL parameters, reducing acquisition time. K_w is sensitive to mannitol-induced changes in BBB permeability and was reduced to 89 ± 17 min⁻¹ in the affected hemisphere compared to 191 ± 22 min⁻¹ in the unaffected hemisphere (P < 0.05). Regions with abnormality in K_w maps were in general agreement with DCE and Evans blue maps, although there are some distinct differences in location and the change in values. Conclusion: K_w is sensitive to mannitol-induced changes in the BBB, with BBB disruption confirmed by DCE MRI and Evans blue histology.