Effects of acetazolamide and caffeine on blood-brain-barrier water permeability measured by non-invasive ASL-based MRI sequences

Motivation: The mechanisms regulating blood-brain-barrier (BBB) function remain largely unknown, especially in neurological disorders. Goal(s): This study aims to use spin-labeling-based MRI sequences to assess changes in cerebral physiology and water transport, induced by pharmacological substances. Approach: Caffeine and acetazolamide were used as pharmacological challenges. Oxygen extraction fraction, perfusion, water extraction fraction(E) and water exchange rate(Kw) were assessed using T2-TRUST, WEPCAST, and T2-prepared pCASL. Results: Both substances strongly affected CBF and OEF while BBB permeability effects were subtler. Water extraction fraction exhibited opposing trends, decreasing with acetazolamide and increasing with caffeine, while Kw increased with acetazolamide and decreased with caffeine. Impact: We demonstrate that the expected physiological effects of caffeine and acetazolamide on brain oxygen extraction fraction, perfusion and BBB function were captured on spin-labeling-based techniques. Combining these drugs and MR-sequences could be useful for research evaluating therapies in neurological disorders.