Respiratory influence on cerebral blood flow and blood volume - A 4D flow MRI study

Abstract

Variations in cerebral blood flow and blood volume interact with intracranial pressure and cerebrospinal fluid dynamics, all of which play a crucial role in brain homeostasis. A key physiological modulator is respiration, but its impact on cerebral blood flow and volume has not been thoroughly investigated. Here we used 4D flow MRI in a population-based sample of 65 participants (mean age = 75 ± 1) to quantify these effects. Two gating approaches were considered, one using respiratory-phase and the other using respiratory-time (i.e. raw time in the cycle). For both gating methods, the arterial inflow was significantly larger during exhalation compared to inhalation, whereas the venous outflow was significantly larger during inhalation compared to exhalation. The cerebral blood volume variation per respiratory cycle was 0.83 [0.62, 1.13] ml for respiratory-phase gating and 0.78 [0.59, 1.02] ml for respiratory-time gating. For comparison, the volume variation of the cardiac cycle was 1.01 [0.80, 1.30] ml. Taken together, our results clearly demonstrate respiratory influences on cerebral blood flow. The corresponding vascular volume variations appear to be of the same order of magnitude as those of the cardiac cycle, highlighting respiration as an important modulator of cerebral blood flow and blood volume.

Keywords: 4D flow MRI; Cerebral blood flow; gating; glymphatic system; respiration.

Figure 1.

Location of flow measurements marked in angiograms from 4D flow MRI data. (a) Example of a location where arterial flow is measured. Internal carotid arteries are marked in red and vertebral arteries are marked in orange and (b) Example of a location where venous flow is measured. Superior sagittal sinus is marked in blue and straight sinus is marked in cyan.

Figure 2.

Illustration of cerebral blood volume variations over the respiratory cycle. (a) Flow rate in arteries (internal carotid arteries and vertebral arteries) over the respiratory cycle. (b) Flow rate in veins (superior sagittal sinus and straight sinus). (c) Net flow to the brain calculated as flow in arteries minus flow in veins. Here the measured venous outflow is multiplied with a constant factor so that the average venous outflow equals the average arterial inflow and (d) blood volume build-up in brain calculated through a cumulative integral of the net flow. The volume variation is the difference between maximum and the minimum of this curve. Here the volume variation is illustrated for respiratory-phase gating.

Figure 3.

Illustration of respiratory gating steps. (a) Signal from respiratory bellows with a low-pass filter. (b) The low-pass filtered signal is subtracted from the respiratory signal and maximum inhalation peaks are marked in red. (c) Complex argument of the Hilbert transformation applied to the filtered respiratory signal and (d) respiratory gating that is linear in time from last inhalation peak.

Figure 4.

Comparison of spoke binning for the two different respiratory gatings. The dots represent spokes for one encode, and alternating colors indicate shifting frame in the respiratory-phase gating. Vertical lines represent frame division for the respiratory-time gating. (a) Frame binning for a relatively symmetrical breathing cycle and (b) frame binning for a breathing cycle with longer exhalation than inhalation.

Figure 5.

Volume variations for two different kinds of respiratory gatings. (a) Comparison of volume variations over the respiratory cycle for respiratory-phase gating vs respiratory-time gating and (b) boxplot of cerebral blood volume variations in the respiratory cycle.

Figure 6.

(a) Average waveforms in arteries over the respiratory cycle for respiratory-phase gating. Individual waveforms are normalized by division of its mean flow. (b) Average waveforms in veins over the respiratory cycle for respiratory-phase gating. Individual waveforms are normalized by division of its mean flow. (c) Average net flow to the brain for respiratory-phase gating. (d) Average volume build-up for respiratory-phase gating. (e) Average waveforms in arteries over the respiratory cycle for respiratory-time gating. Individual waveforms are normalized by division of its mean flow. (f) Average waveforms in veins over the respiratory cycle for respiratory-time gating. Individual waveforms are normalized by division of its mean flow. (g) Average net flow to the brain for respiratory-time gating and (h) average volume build-up for respiratory-time gating. The error-bars for all plots are given as 95% confidence interval for the mean, with ±2SD/ $\sqrt{\mathrm{n}}$ .