Multivariate dynamic analysis of cerebral blood flow regulation in humans

Abstract

The contributions of beat-to-beat changes in mean arterial blood pressure (MABP) and breath-by-breath fluctuations in end-tidal CO2 (EtCO2) as determinants of the spontaneous variability of cerebral blood flow velocity (CBFV) were studied in 16 normal subjects at rest. The two input variables (MABP and EtCO2) had significant cross-correlations with CBFV but not between them. Transfer functions were estimated as the multivariate least mean square finite impulse response causal filters. MABP showed a very significant effect in explaining CBFV variability (p< 10(-11), Fisher's aggregated-p test) and the model mean square error was significantly reduced (p < 0.001) by also including the contribution of EtCO2. The estimated mean CBFV step response to MABP displayed the characteristic return to baseline caused by the cerebral autoregulatory response. The corresponding response to EtCO2 showed a gradual rise taking approximately 10 s to reach a plateau of 2.5%/mmHg. This study demonstrated that spontaneous fluctuations in EtCO2 can help to explain the CBFV variability at rest if appropriate signal processing techniques are employed to address the limited power and bandwith of the breath-by-breath EtCO2 signal.

Adaptive feedback analysis and control of programmable stimuli for assessment of cerebrovascular function

“…The former maintains cerebral blood flow (CBF) relatively constant despite changes in mean arterial blood pressure (ABP) and the latter reflects the strong effects that changes in PaCO 2 can have on CBF. Many previous studies using system identification techniques to investigate CBF regulatory mechanisms were based on spontaneous fluctuations of ABP (as input) and CBF (as output) to extract information about the dynamic properties of cerebral autoregulation in the frequency or time-domain [3,4,5], and such modeling has also been extended to CO2 reactivity [3,5]. Despite the many advantages of using spontaneous physiological fluctuations in the input and output signals, this approach has several limitations, chiefly the reliability of model based estimates due to poor signal-to-noise ratio and narrow band spectral distributions.…”

Optimising the assessment of cerebral autoregulation from black box models

“…Even though studies including multivariate models have been published [30,35], so far there has been little analysis as to whether this type of models may offer an improvement in terms of separation between normal and impaired conditions compared to the univariate approaches.…”

Modelling cerebral blood flow autoregulation in humans

“…Further insight into the sub-systems depicted in Fig. 1 could be gained by multivariate modelling, as shown by preliminary studies [34,45,46], but the technical difficulties in this area should not be underestimated [34].…”

“…1 are assumed to be inside a single "black-box". Nevertheless, this approach provides CBFV step responses to ABP changes that represent a relatively simple method to assess cerebral autoregulation in a clinical setting, using spontaneous fluctuations in ABP [29][30][31][32][33][34][35][36]. Tiecks et al [5] proposed a second order system to model the relationship between CBF velocity (CBFV) and ABP during transients produced by the sudden release of inflated thigh cuffs.…”

“…The main objective of the model was to estimate a single parameter, the autoregulation index (ARI), that can reflect the "strength of dynamic autoregulation" [5]. The step response technique also allows a practical way to take into account the interaction between CO2 and cerebral autoregulation [31,34]. CBFV step responses estimated from ABP transients induced by manoeuvres that stimulate the autonomic nervous system, suggest that sympathetic activity does not influence cerebral autoregulation in the normal range of mean ABP [36].…”