Cerebral blood flow response to acute hypoxic hypoxia

Abstract

Hypoxic hypoxia (inspiratory hypoxia) stimulates an increase in cerebral blood flow (CBF) maintaining oxygen delivery to the brain. However, this response, particularly at the tissue level, is not well characterised. This study quantifies the CBF response to acute hypoxic hypoxia in healthy subjects. A 20-min hypoxic (mean P(ETO2) = 52 mmHg) challenge was induced and controlled by dynamic end-tidal forcing whilst CBF was measured using pulsed arterial spin labelling perfusion MRI. The rate constant, temporal delay and magnitude of the CBF response were characterised using an exponential model for whole-brain and regional grey matter. Grey matter CBF increased from 76.1 mL/100 g/min (95% confidence interval (CI) of fitting: 75.5 mL/100 g/min, 76.7 mL/100 g/min) to 87.8 mL/100 g/min (95% CI: 86.7 mL/100 g/min, 89.6 mL/100 g/min) during hypoxia, and the temporal delay and rate constant for the response to hypoxia were 185 s (95% CI: 132 s, 230 s) and 0.0035 s(-1) (95% CI: 0.0019 s(-1), 0.0046 s(-1)), respectively. Recovery from hypoxia was faster with a delay of 20 s (95% CI: -38 s, 38 s) and a rate constant of 0.0069 s(-1) (95% CI: 0.0020 s(-1), 0.0103 s(-1)). R2*, an index of blood oxygenation obtained simultaneously with the CBF measurement, increased from 30.33 s(-1) (CI: 30.31 s(-1), 30.34 s(-1)) to 31.48 s(-1) (CI: 31.47 s(-1), 31.49 s(-1)) with hypoxia. The delay and rate constant for changes in R2 * were 24 s (95% CI: 21 s, 26 s) and 0.0392 s(-1) (95% CI: 0.0333 s(-1), 0.045 s(-1)), respectively, for the hypoxic response, and 12 s (95% CI: 10 s, 13 s) and 0.0921 s(-1) (95% CI: 0.0744 s(-1), 0.1098 s(-1)/) during the return to normoxia, confirming rapid changes in blood oxygenation with the end-tidal forcing system. CBF and R2* reactivity to hypoxia differed between subjects, but only R2* reactivity to hypoxia differed significantly between brain regions.

Keywords: R2*; arterial spin labelling (ASL); blood oxygenation; cerebral blood flow (CBF); cerebral perfusion; hypoxia; temporal dynamics.

Figure 1

Schematic diagram of modelling parameters. This model was used for both the cerebral blood flow (CBF) and R₂* time series but, for descriptive purposes, we refer here to CBF only. CBF_B is the CBF calculated during the baseline period, and CBF_H and CBF_R are the equilibrium CBF values obtained during hypoxia and recovery, respectively. The rate constants during the transition to hypoxia and back to normoxia during the recovery are denoted by k_H and k_R, respectively, and these transitions occur at delays of δ_H and δ_R after the gas mixtures are switched to the hypoxic challenge or back to normoxia, respectively.

Figure 2

Sample cerebral blood flow (CBF) maps from one individual during normoxic baseline (a), hypoxic hypoxia (b) and normoxic recovery (c). Each map is derived from 5 min of data and has been registered to MNI space. CBF is displayed in mL/100 g tissue/min.

Figure 3

Group-averaged end-tidal O₂ (black) and CO₂ (grey).

Figure 4

Cerebral blood flow (CBF) and R₂* across whole-brain grey matter. Quantified CBF and the CBF modelled response are shown in light green and dark green, respectively. R₂* over time and the modelled response are shown in pink and red, respectively. The time-series data for CBF and R₂* were averaged into 11-s time bins for display purposes.