Phase seems an age independent autoregulatory index. In controlled HBP, CBF regulation is degraded at longlasting CBF changes; BPV effects lose their physiological bilateral distribution.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

Objectives: At present, there is no standard bedside method for assessing cerebral autoregulation (CA) with high temporal resolution. We combined the two methods most commonly used for this purpose, transcranial Doppler sonography (TCD, macro-circulation level), and near-infrared spectroscopy (NIRS, micro-circulation level), in an attempt to identify the most promising approach.Methods: In eight healthy subjects (5 women; mean age, 38 ± 10 years), CA disturbance was achieved by adding carbon dioxide (CO2) to the breathing air. We simultaneously recorded end-tidal CO2 (ETCO2), blood pressure (BP; non-invasively at the fingertip), and cerebral blood flow velocity (CBFV) in both middle cerebral arteries using TCD and determined oxygenated and deoxygenated hemoglobin levels using NIRS. For the analysis, we used transfer function calculations in the low-frequency band (0.07–0.15 Hz) to compare BP–CBFV, BP–oxygenated hemoglobin (OxHb), BP–tissue oxygenation index (TOI), CBFV–OxHb, and CBFV–TOI.Results: ETCO2 increased from 37 ± 2 to 44 ± 3 mmHg. The CO2-induced CBFV increase significantly correlated with the OxHb increase (R2 = 0.526, p < 0.001). Compared with baseline, the mean CO2 administration phase shift (in radians) significantly increased (p < 0.005) from –0.67 ± 0.20 to –0.51 ± 0.25 in the BP–CBFV system, and decreased from 1.21 ± 0.81 to −0.05 ± 0.91 in the CBFV–OxHb system, and from 0.94 ± 1.22 to −0.24 ± 1.0 in the CBFV–TOI system; no change was observed for BP–OxHb (0.38 ± 1.17 to 0.41 ± 1.42). Gain changed significantly only in the BP–CBFV system. The correlation between the ETCO2 change and phase change was higher in the CBFV–OxHb system [r = −0.60; 95% confidence interval (CI): −0.16, −0.84; p < 0.01] than in the BP–CBFV system (r = 0.52; 95% CI: 0.03, 0.08; p < 0.05).Conclusion: The transfer function characterizes the blood flow transition from macro- to micro-circulation by time delay only. The CBFV–OxHb system response with a broader phase shift distribution offers the prospect of a more detailed grading of CA responses. Whether this is of clinical relevance needs further studies in different patient populations.

Objectives: The dynamic interaction between blood pressure (BP) and cerebral blood flow velocity (CBFV) is not fully understood, especially for CBFV changes lasting longer than 50 s. The interaction between BP and CBFV is relatively well characterized for periods <50 s using transfer function (TF) estimations of phase, gain, and coherence. We used TF estimations to compare the phase and gain for periods >50 s with those for periods <50 s.Materials and Methods: BP and CBFV (of the middle cerebral artery) were simultaneously recorded in 23 healthy subjects (10 men, 13 women, mean age 35 ± 10 years) under normo- and hypocapnia (induced by hyperventilation). TF and coherence estimations were based on Welch's periodogram method with a windowing of 200 s (frequency resolution, 0.005 Hz, corresponding to a period of 200 s). Means of the phase, gain, and coherence were calculated over frequency periods of 0.005–0.02 Hz (sVLF), 0.02–0.07 Hz (VLF), 0.07–0.15 Hz (LF), and 0.15–0.40 Hz (HF) and analyzed using the t-test and Pearson correlation.Results: Compared with the VLF range, normo- and hypocapnia phases were slightly but significantly lower in sVLF, while gain and coherence were not different. Hypocapnia induced significant (mostly p < 0.01) phase increases and gain decreases as well as coherence decreases in all frequency ranges. The phase and gain correlated significantly (−0.87 < r > −0.99) (p < 0.001) and inversely in all frequency ranges <0.15 Hz under both respiratory conditions. In some instances, the phase indicated disturbed autoregulation.Conclusion: In the frequency range <0.15 Hz, the phase and gain correlate highly and linearly with high consistency. The phase, gain, and coherence were similar in sVLF and VLF ranges. The phase was slightly lower in the sVLF range than in the VLF range. Notably, the data suggest that autoregulatory failure may occur in healthy persons.

CTA analysis with a semiautomated vessel analysis tool provides variable results. Large discrepancies between methods in the degree of reported stenosis must be taken into consideration when CTA and DUS are used for clinical purposes. The semiautomated software tools need further improvements.

the mechanisms of high blood pressure (HBp)-related brain pathology progression remain relatively unclear. We investigated whether lowering BP in chronic HBP patients normalizes cerebral perfusion dynamics at resistance vessel and capillary levels. Sixty-seven patients with HBP and 49 age-and sexmatched healthy controls underwent simultaneous recordings of middle cerebral artery blood flow velocity (cBfV), Bp, and end-tidal co 2 concentration. Thirty-four controls and 28 patients underwent additional near-infrared spectroscopy recordings (oxygenated [o 2 Hb] and deoxygenated [HHb] hemoglobin). Degree of microcirculatory white matter lesions was graded by Fazekas scale. Dynamic cerebral autoregulation (dCA) was assessed by transfer function analysis. BP was successfully lowered (patients = 89 ± 15 mm Hg, controls = 87 ± 17), but cerebrovascular resistance was higher in BP patients (p < 0.05). BP-CBFV phase was lower in very low frequency (VLF) (left/right: 48 ± 20°/44 ± 17; controls: 61 ± 20/60 ± 21; p < 0.001) and low frequency (LF) (34 ± 14/35 ± 14; controls: 48 ± 20/44 ± 17; p < 0.05) ranges. Gain was higher in VLF range (in %/ mm Hg 0.56 ± 0.44/0.59 ± 0.49; controls: 0.32 ± 0.29/0.34 ± 0.32; p ≤ 0.005). BP-CBFV phase and gain did not differ across Fazekas groups. Across all patients, the capillary phases and gains (CBFV-[O2Hb], CBFV-[HHb]) were comparable to controls. Successfully treated chronic HBP results in normal brain capillary hemodynamics while the resistance vessel state is disturbed (phase decrease, gain increase). The cerebral consequences of chronic high blood pressure (HBP) are manifold: the most frequent are hemorrhagic and nonhemorrhagic stroke, cerebral small vessel disease with white matter lesions (WML), microbleeds, or brain atrophy which can lead to cognitive decline and dementia 1. Small vessel disease has also been reported to contribute to the pathogenesis of Alzheimer's disease 2,3. The pathological mechanisms of HBP-related brain pathology progression, however, are unclear. Among others, a constant elevated level of mean systolic or diastolic BP and their variabilities 4,5 , autonomic BP regulation disturbances 6 , increased pulse pressure amplitudes 7 , ischemic effects on the brain due to cerebral autoregulation (CA) failure 8-11 , and capillary dysfunction 12 are proposed mechanisms of continuous cerebral tissue damage. More recently, aging is assumed to accelerate the HBP-driven pathologies 3,13. Cerebral blood flow is determined by BP-dependent regulatory effects and by metabolic influences on the resistance vessels via feedback mechanisms. These regulatory mechanisms can be observed noninvasively by cerebral blood flow velocity (CBFV) and its wave form, and by changes in the microcirculatory concentrations of oxygenated and deoxygenated hemoglobin (Hb) via near-infrared spectroscopy (NIRS) 14-16. Anatomically, CBFV mirrors the regulatory effects in front of the resistance vessel in the large (macrocirculatory) brain supplying arteries such as the middle cerebral artery, while the...