Mapping of the cerebral response to acetazolamide using graded asymmetric spin echo EPI

Abstract

Cerebral vascular reactivity in different regions of the rat brain was quantitatively characterized by spatial and temporal measurements of blood oxygenation level-dependent (BOLD)-fMRI signals following intravenous administration of the carbonic anhydrase inhibitor acetazolamide: this causes cerebral vasodilatation through a cerebral extracellular acidosis that spares neuronal metabolism and vascular smooth muscle function, thus separating vascular and cerebral metabolic events. An asymmetric spin echo-echo planar imaging (ASE-EPI) pulse sequence sensitised images selectively to oxygenation changes in the microvasculature; use of a surface coil receiver enhanced image signal-to-noise ratios (SNRs). Image SNRs and hardware integrity were verified by incorporating quality assurance procedures; cardiorespiratory stability in the physiological preparations were monitored and maintained through the duration of the experiments. These conditions made it possible to apply BOLD contrast fMRI to map regional changes in cerebral perfusion in response to acetazolamide administration. Thus, fMRI findings demonstrated cerebral responses to acetazolamide that directly paralleled the known physiological actions of acetazolamide and whose time courses were similar through all regions of interest, consistent with acetazolamide's initial distribution in brain plasma, where it affects cerebral haemodynamics by acting at cerebral capillary endothelial cells. However, marked variations in the magnitude of the responses suggested relative perfusion deficits in the hippocampus and white matter regions correlating well with their relatively low vascularity and the known vulnerability of the hippocampus to ischaemic damage.