title: 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.
authors.affiliation: CUBRIC, School of Psychology, Cardiff University, Cardiff, UK.
authors.forename: Ashley D
authors.initials: AD
authors.lastname: Harris
authors.forename: Kevin
authors.initials: K
authors.lastname: Murphy
authors.forename: Claris M
authors.initials: CM
authors.lastname: Diaz
authors.forename: Neeraj
authors.initials: N
authors.lastname: Saxena
authors.forename: Judith E
authors.initials: JE
authors.lastname: Hall
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Liu
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wise
mesh_terms: D000208:Acute Disease; D000328:Adult; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008954:Models, Biological
keywords: R2*; arterial spin labelling (ASL); blood oxygenation; cerebral blood flow (CBF); cerebral perfusion; hypoxia; temporal dynamics