Pharmacological modulation of the BOLD response: a study of acetazolamide and glyceryl trinitrate in humans

Abstract

Purpose: To examine the effect of acetazolamide, known to increase cerebral blood flow (CBF) and glyceryl trinitrate (GTN), known to increase cerebral blood volume (CBV) on the blood oxygenation level-dependent (BOLD) response in humans using 3 T magnetic resonance imaging (MRI), and to evaluate how pharmacological agents may modulate cerebral hemodynamic and thereby possibly the BOLD signal.

Materials and methods: Six subjects were randomly allocated to receive acetazolamide, GTN, or placebo in a double-blind three-way crossover controlled study. Before, during, and after drug administration we recorded the BOLD response during visual stimulation with reversing checkerboard.

Results: We found that acetazolamide caused significant depression of the BOLD response (P = 0.0066). The maximum decrease occurred at 5 minutes after infusion and was 51.9% (95% confidence interval [CI], 22.03-81.76). GTN did not influence the BOLD response (P = 0.55).

Conclusion: The BOLD response is decreased during increased CBF by acetazolamide, suggesting an inverse relationship between global CBF and the BOLD response. GTN does not change the BOLD response. This indicates that GTN exerts an effect on the large vessels only and that CBV changes in the microvascular system are necessary to alter the BOLD response.