A multimodality investigation of cerebral haemodynamics and autoregulation in phMRI

Results: Baseline MABP levels were equivalent in all treatment groups (overall mean 94.0±12 mmHg). Increasing doses of NE (0.125, 0.5, 2 and 8 µg/ml) produced transient, dose-dependent rises in MABP (96±14, 121±13, 152±27 and 174±17 mmHg at peak, respectively, Fig 1A). At the three highest doses the effect reached statistical significance (p<0.01, p<0.05 and p<0.001 at peak vs. saline, respectively). No significant changes in LDF were observed with MABP increases up to 130 mmHg (NE 0.5 ug/kg, Fig 1B). Larger MABP increases (NE 2 and 8 ug/kg) gave rise to a marked increase in LDF (+30% and +37%, respectively), thus indicating a breakdown in blood flow autoregulation for large MABP responses (p<0.001 and p<0.01 at peak, respectively, Fig 1B). The two highest doses of NE also induced a transient increase in rCBV (p<0.05, Fig 1C). Interestingly, the concomitant changes in rCBV were mainly localised in cortical structures of the brain (Fig 1D). Discussion: Whether autoregulation is preserved under anaesthesia has been a contentious matter in recent literature with often inconsistent results, possibly because autoregulation is sensitive to the specific experimental conditions [8,9]. Here we have measured independently MABP, CBF and CBV changes induced by acute challenge with a drug that does not cross the BBB, and therefore is not expected to elicit changes in neuronal activity. The challenge was administered intravenously, thus inducing a rapid cardiovascular response that closely mimics the profile of MABP changes observed in phMRI experiments using this route of administration. The LDF data demonstrated that CBF autoregulation was preserved under our experimental conditions over a wide range of pressure changes. Moreover, our data suggest that with MABP changes within the CBF autoregulatory range, the concomitant CBV changes are smaller than previously reported [10]. This finding is in good agreement with the results of Zaharchuk et al. [11], which observed small and non-significant CBV changes when the MABP was decreased from 140 down to 50 mmHg under experimental conditions very similar to those of our study. Above a certain MABP threshold, autoregulation breaks down, and measurable changes in both rCBF and rCBV were observed. Interestingly, in this regime, changes in rCBV were not uniformly widespread in the brain, but showed a certain degree of regionalisation particularly in cortical structures, possibly reflecting higher vascular density.