Effects of Acetazolamide on Cerebral Blood Flow, Blood Volume, and Oxygen Metabolism: A Positron Emission Tomography Study with Healthy Volunteers

Abstract

To evaluate changes in cerebral hemodynamics and metabolism induced by acetazolamide in healthy subjects, positron emission tomography studies for measurement of cerebral perfusion and oxygen consumption were performed. Sixteen healthy volunteers underwent positron emission tomography studies with 15O-gas and water before and after intravenous administration of acetazolamide. Dynamic positron emission tomography data were acquired after bolus injection of H2[15O] and bolus inhalation of 15O2. Cerebral blood flow, metabolic rate of oxygen, and arterial-to-capillary blood volume images were calculated using the three-weighted integral method. The images of cerebral blood volume were calculated using the bolus inhalation technique of C[15O]. The scans for cerebral blood flow and volume and metabolic rate of oxygen after acetazolamide challenge were performed at 10, 20, and 30 minutes after drug injection. The parametric images obtained under the two conditions at baseline and after acetazolamide administration were compared. The global and regional values for cerebral blood flow and volume and arterial-to-capillary blood volume increased significantly after acetazolamide administration compared with the baseline condition, whereas no difference in metabolic rate of oxygen was observed. Acetazolamide-induced increases in both blood flow and volume in the normal brain occurred as a vasodilatory reaction of functioning vessels. The increase in arterial-to-capillary blood volume made the major contribution to the cerebral blood volume increase, indicating that the raise in cerebral blood flow during the acetazolamide challenge is closely related to arterial-to-capillary vasomotor responsiveness.

Arterial Spin-Labeling Evaluation of Cerebrovascular Reactivity to Acetazolamide in Healthy Subjects

“…18 The administration of ACZ may shorten the arrival time as a result of increased blood velocity and aid early influx of labeled water into the brain tissues, which may enhance ASL signals with a short PLD preferentially and consequently cause overestimation of CVR. The mean CVR values reported in normal subjects range from 25-31% with the use of 133 Xe inhalation SPECT, 18,21-23 from 33.5-35% with the use of 15 O-water positron-emission tomography, 24,25 and from 37.7-54.2% with the use of ASL MR imaging. [9][10][11] Although the CVR values obtained with the use of a PLD of either 1525 ms (43.8 -46.4%, depending on the region) or 2525 ms (26.9 -32.5%) in the present study are in the range of the reported values, those obtained with a PLD of 1525 ms as well as those previously reported by use of ASL MR imaging are relatively high; thus, ASL MR imaging probably leads to overestimation of CVR.…”

Changes in the Arterial Fraction of Human Cerebral Blood Volume during Hypercapnia and Hypocapnia Measured by Positron Emission Tomography

“…Because V a includes the blood volume of cerebral arterioles, our results correspond well to these previous observations. In addition, an increase in V a during acetazolamide stress has also been observed in human brain (Okazawa et al, 2001). V c is considered to be negligibly small (Mintun et al, 1984); however, V c in the living human brain is unknown.…”

BOLD and Perfusion Response to Finger-Thumb Apposition after Acetazolamide Administration: Differential Relationship to Global Perfusion

“…2. Because the exponential term in Grubb's power law relating flow to blood volume is less than 1, the finding that acetazolamide alters CBF more than CBV (Okazawa et al, 2001) implies that acetazolamide administration would reduce M, causing %BOLD to decline. The restricted dynamic range account of the relationship between %BOLD and resting perfusion explains the diminished BOLD response as a result of a floor effect for deoxyhemoglobin concentration under conditions of high resting CBF.…”