Ultra-fast magnetic resonance encephalography of physiological brain activity - Glymphatic pulsation mechanisms?

Abstract

The theory on the glymphatic convection mechanism of cerebrospinal fluid holds that cardiac pulsations in part pump cerebrospinal fluid from the peri-arterial spaces through the extracellular tissue into the peri-venous spaces facilitated by aquaporin water channels. Since cardiac pulses cannot be the sole mechanism of glymphatic propulsion, we searched for additional cerebrospinal fluid pulsations in the human brain with ultra-fast magnetic resonance encephalography. We detected three types of physiological mechanisms affecting cerebral cerebrospinal fluid pulsations: cardiac, respiratory, and very low frequency pulsations. The cardiac pulsations induce a negative magnetic resonance encephalography signal change in peri-arterial regions that extends centrifugally and covers the brain in ≈1 Hz cycles. The respiratory ≈0.3 Hz pulsations are centripetal periodical pulses that occur dominantly in peri-venous areas. The third type of pulsation was very low frequency (VLF 0.001-0.023 Hz) and low frequency (LF 0.023-0.73 Hz) waves that both propagate with unique spatiotemporal patterns. Our findings using critically sampled magnetic resonance encephalography open a new view into cerebral fluid dynamics. Since glymphatic system failure may precede protein accumulations in diseases such as Alzheimer's dementia, this methodological advance offers a novel approach to image brain fluid dynamics that potentially can enable early detection and intervention in neurodegenerative diseases.

Keywords: Resting state; blood oxygen level dependent; cardiorespiratory; glymphatics; magnetic resonance encephalography.

Figure 1.

Illustration of the iterative QPP algorithm procedure in the detection of both periodic and quasi-periodic physiological brain pulsations.

Figure 2.

Illustrates two blue MREG Fast Fourier Transform (FFT) power spectra of a ventromedial DMN_vmpf MREG time signal after PICA-dual regression. The upper presents power till 5 Hz (cut-off 3.2–4.8 Hz) and below between 0–0.2 Hz. Respiratory frequency clusters around 0.37 Hz and cardiac frequency peaks at 1.08 Hz in MREG data, which are identical to pneumatic respiratory monitoring belt and FFT power spectra of ECG data shown in black. The cardiorespiratory pulsations have harmonic peaks at higher frequencies both in MREG and physiological verification data. VLF (0.01–0.027 Hz) and LF (0.027–0.73 Hz) bands present highest power peaks in the spectrum. NIBP data are shown to illustrate VLF/LF spectral power of the mean arterial blood pressure waves. The filtered MREG time domain signals are presented (blue), cardiorespiratory signals with 10 × shorter window than the VLF/LF signals. Individual QPP_maps are presented next to corresponding physiological signals.

Figure 3.

Group averaged time domain z-score signal change in the selected ROI's in 2 mm MNI space (coordinates in brackets) with in-plane T1-weighted image showing each ROI. Percent MREG signal change ( ± std) of the average regional pulse wave amplitude is shown in black. The cardiac impulse (top left) locked with the cardiac systole induces a markedly symmetric pulse between hemispheres and in the anterior–posterior direction but alters in phase in periarterial areas and in basal CSF areas near the circle of Willis. The respiratory (top right) pattern of the brain averaged into a 3.7 s cycle shows the slower effect to be more pronounced in cortical areas than in the white matter. The highest amplitudes were detected in pons and CSF areas. Quasi-periodic LF (37 s) and VLF (100 s time window) waves show the lack of temporal periodicity in basal areas and CSF areas but have more repeating pulsations in the cortex. Also note that all data are averaged and phase corrected to match subj # 9's QPP_map data.

Figure 4.

3D time lapsed group averaged and phase-matched QPP_maps of physiological pulsations of the human brain. The cardiac impulse triggered by systole (ECG R-peak) shows a negative impulse starting from arteries and extending via ventricles into brain parenchyma. Next to cardiac is the respiratory cycle presenting a positive MREG signal change during inspiration. The LF and VLF waves are shown in 37 s and 100 periods matching DMN_vmpf signal sources, respectively. The color encoding represents normalized z-score from 0.05 to 1 yellow (negative in blue) in FSL MNI 152 2 mm space (x, y, z coordinates 0, 36, −14). For a better view of the dynamical nature of the pulsations, c.f. supplementary material S1 for 3D NI-video.

Figure 5.

Anatomical MNI image with arrows pointing to the propagation direction of the first pulse effect, blue indicates negative and red-orange positive MREG-signal change. The cardiac impulse on top has timed negative post-systolic changes, which are cyclically followed by positive counter pulse effect in the same direction. The inspiration effects introduce a positive centripetal pulsation marked with double headed arrows. The LF waves induce wider and more uniform patterns extending to white matter. At the bottom, the VLF waves have both uniform, widespread pulses that intermittently mix with resting-state network patterns. Moreover, the VLF waves move in opposing directions compared to other pulses, c.f. initial blue wave going towards occipital areas followed by positive yellow direction towards the front.