Multimodal pressure-flow method to assess dynamics of cerebral autoregulation in stroke and hypertension

Abstract

Background: This study evaluated the effects of stroke on regulation of cerebral blood flow in response to fluctuations in systemic blood pressure (BP). The autoregulatory dynamics are difficult to assess because of the nonstationarity and nonlinearity of the component signals.

Methods: We studied 15 normotensive, 20 hypertensive and 15 minor stroke subjects (48.0 +/- 1.3 years). BP and blood flow velocities (BFV) from middle cerebral arteries (MCA) were measured during the Valsalva maneuver (VM) using transcranial Doppler ultrasound.

Results: A new technique, multimodal pressure-flow analysis (MMPF), was implemented to analyze these short, nonstationary signals. MMPF analysis decomposes complex BP and BFV signals into multiple empirical modes, representing their instantaneous frequency-amplitude modulation. The empirical mode corresponding to the VM BP profile was used to construct the continuous phase diagram and to identify the minimum and maximum values from the residual BP (BPR) and BFV (BFVR) signals. The BP-BFV phase shift was calculated as the difference between the phase corresponding to the BPR and BFVR minimum (maximum) values. BP-BFV phase shifts were significantly different between groups. In the normotensive group, the BFVR minimum and maximum preceded the BPR minimum and maximum, respectively, leading to large positive values of BP-BFV shifts.

Conclusion: In the stroke and hypertensive groups, the resulting BP-BFV phase shift was significantly smaller compared to the normotensive group. A standard autoregulation index did not differentiate the groups. The MMPF method enables evaluation of autoregulatory dynamics based on instantaneous BP-BFV phase analysis. Regulation of BP-BFV dynamics is altered with hypertension and after stroke, rendering blood flow dependent on blood pressure.

Figure 1

Schematic diagram showing Hilbert-Huang decomposition of the original blood pressure (BP) signal into the empirical modes corresponding to amplitude-frequency modulation for different time scales. Panel A shows the profile of the BP waveform over the course of the VM: I- indicates the beginning of the maneuver, II- the duration of straining, III-the end of straining and IV- the BP overshoot above baseline. (Note that the transient BP decrease in phase III is due to inspiration.) Panel B shows the empirical modes for each component frequencies and their corresponding amplitudes were detected from the signal (mode 1–10). Empirical modes corresponding to the faster frequencies (modes 1–5) were removed from the original BP and BFV signals. The empirical mode corresponding to the characteristic BP profile induced by the VM (BP_VM – mode 6 in this example) was used to obtain phase information. Modes 7–10 reflect BP modulations at slow frequencies. Similarly, the empirical mode corresponding to the characteristic BFV profile was extracted from the raw BFV waveform (not shown).

Figure 2

Panel A shows blood pressure (BP) and blood flow velocity (BFV) waveforms from the right and left MCAs (MCAR and MCAL respectively) during the VM for a normotensive subject (top 3 panels). The duration of the VM straining is indicated by a horizontal line. The thick black line indicates the BP_R and BFV_R that reflect the characteristic VM oscillation. Bottom 3 panels show BP_R and BFV_R in the MCAR and MCAL. Arrows indicate phases at the BP_R and BFV_R minima. With normal autoregulation, BFV_R minimum preceded BP_R minimum. Panel B shows BP and BFV waveforms for a subject with a left temporal infarct (MCAR = non stroke-side MCA, MCAL = stroke side MCA) (top 3 panels). Horizontal line indicates duration of the VM. Black thick line indicates the BP_R and BFV_R obtained from the BP and BFV raw waveforms. Bottom 3 panels show BP_R and BFV_R in the non-stroke side MCA and in the stroke-side MCA expressed as a function of BP_VM phase. Arrows indicate that the phase at BFV minimum was similar to the phase at BP minimum.

Figure 3

Panel A shows the phase and corresponding residual blood flow velocity (BFV_R) values at baseline, BFV_R minimum and BFV_R maximum for the right MCA for the normotensive -●- and - -▼- hypertensive groups and for - O- the non-stroke side MCA in the stroke group. Panel B shows the phase and corresponding BFV_R values for the left MCA in the normotensive and hypertensive groups and for the stroke side MCA in the stroke group. BFV_R phase was significantly greater in the stroke and hypertensive groups compared to the normotensive group for BFV_R minimum and maximum in both MCAs (between groups phase comparisons *** p < 0.005, ** p < 0.01). Panel C shows the phase and corresponding residual blood pressure (BP_R) values for the BP_R minimum and maximum (between groups BP_R values comparisons +++ p < 0.001, mean ± SE).

Figure 4

Panel A shows the phase shift between BP_R minimum and BFV_R minimum and the phase shift between BP_R maximum and BFV_R maximum for the right MCA for the □ normotensive and hypertensive groups and ■ for the non-stroke side MCA in the stroke group. Figure 4B shows the phase shift between BP_R minimum and BFV_R minimum and the phase shift between BP_R maximum and BFV_R maximum for the left MCA for the normotensive, and hypertensive groups and for the stroke side MCA in the stroke group. Phase shift was greater in the normotensive compared to other groups (between group comparisons *** p < 0.005, ** p < 0.01 *p < 0.05, mean ± SE).