Synchronous assessment of CSF and cerebral arteriovenous flow interactions across ultra-low, low, respiratory, and cardiac frequencies using real-time phase-contrast MRI.

Cerebrospinal fluid (CSF) oscillations are traditionally viewed as passive responses to cardiac-driven cerebral blood volume (CBV) fluctuations. However, the origins of their respiratory, low-, and ultra-low-frequency components remain unclear. This study employed a single-VENC (30 cm/s), long-duration (∼4 min) real-time phase-contrast MRI (RT-PC) protocol to synchronously quantify cerebral blood and CSF flows across multiple frequency bands, aiming to identify the primary drivers of CSF oscillations. In seven healthy adults, arterial, venous, and CSF flows were simultaneously acquired at the C2-C3 level under free-breathing conditions. After image segmentation, background correction, and flow integration, CBV and CSF volume displacement (CSFV) curves were derived and spectrally decomposed into ultra-low (0.01-0.05 Hz), low (0.05-0.1 Hz), respiratory (∼0.3 Hz), and cardiac (∼1 Hz) bands. Mean amplitudes (±SD, ml) in the ultra-low, low, respiratory, and cardiac bands were as follows: for CBV, 4.6 ± 2.0, 1.1 ± 0.5, 1.3 ± 0.9, and 0.8 ± 0.1; for CSFV, 1.9 ± 0.5, 0.8 ± 0.2, 0.5 ± 0.2, and 0.6 ± 0.2. Notably, CBV amplitude in the ultra-low band exhibited a bimodal distribution potentially linked to sleep state. Cross-correlation analysis revealed mirrored CBV-CSFV coupling across all frequency bands, ranging from moderate (ultra-low and low: -0.59) to strong correlation (cardiac: -0.88, respiratory: -0.91). However, band-specific lags indicated distinct underlying mechanisms. Cardiac oscillations (CBV leading CSFV; lag = -0.18 ± 0.08 s, p < 0.01) aligned with pressure-driven models. Low-frequency oscillations (CSFV preceding CBV; lag = 0.81 ± 0.67 s, p = 0.03) suggested cerebrovascular reactivity (CVR) mediated compliance changes. Respiratory oscillations showed near-synchronous coupling (lag = -0.13 ± 0.41 s, not significant), likely reflecting combined CBV and CVR effects. In the ultra-low-frequency band, CSFV led CBV by 5-8 seconds in over half of the data, potentially reflecting a complex neuro-respiratory regulatory pathway. This study demonstrates the feasibility of RT-PC for synchronous quantification of cerebral blood and CSF dynamics. Our findings reveal that CSF oscillations are driven not only by CBV fluctuations but also by CVR-modulated changes in brain compliance. These results provide novel insights into frequency-dependent neurofluid coupling, offering a physiological foundation for disease understanding and diagnostic development in neurological disorders.