Dynamic cerebral autoregulation reproducibility is affected by physiological variability

Parameters describing dynamic cerebral autoregulation (DCA) have limited reproducibility. 59 In an international, multi-centre study, we evaluated the influence of multiple analytical 60 methods on the reproducibility of DCA. Fourteen participating centers analyzed repeated 61 measurements from 75 healthy subjects, consisting of five minutes of spontaneous 62 fluctuations in blood pressure (BP) and cerebral blood flow velocity (CBFv) signals, based on 63 their usual methods of analysis. DCA- methods were grouped into three broad categories, 64 depending on output types: 1. Transfer function analysis (TFA); 2. Autoregulation index 65 (ARI); and 3. correlation coefficient. Only TFA gain in the low frequency (LF) band showed 66 good reproducibility in approximately half of the estimates of gain, defined as an intraclass 67 correlation coefficient (ICC) of > 0.6. None of the other DCA metrics had good 68 reproducibility. For TFA-like and ARI-like methods, ICCs were lower than values obtained 69 with surrogate data (p<0.05). For TFA-like methods, ICCs were lower for the very low 70 frequency (VLF) band (gain 0.38 ± 0.057, phase 0.17 ± 0.13) than for LF band (gain 0.59 ± 71 0.078, phase 0.39 ± 0.11, p≤0.001 for both gain and phase). For ARI-like methods, the mean 72 ICC was 0.30 ± 0.12 and for the correlation methods 0.24 ± 0.23. Based on comparisons with 73 ICC estimates obtained from surrogate data, we conclude that physiological variability or 74 non-stationarity is likely to be the main reason for the poor reproducibility of DCA 75 parameters