Quantitative evaluation of low-frequency oscillations using real-time phase-contrast MRI during drowsiness

Low-frequency oscillations (LFOs) in the brain are increasingly recognized for their role in driving brain clearance during sleep and drowsiness. However, human studies have largely relied on qualitative assessment. Quantitative assessments of LFO-driven flow dynamics remain limited, and findings across animal and human studies are mixed. Some report that ventricular CSF inflow is dominated by LFO activity, whereas others suggest that cardiac pulsations are the primary driver of CSF motion along its circulation pathways. In this study, we employed real-time phase-contrast (RT-PC) MRI to quantitatively measure blood and cerebrospinal fluid (CSF) flow rates at the cervical level. Our goal was to assess contributions of LFOs across vascular and CSF compartments and to examine their changes between wakefulness and drowsiness. RT-PC MRI was acquired at the cervical (C2/C3) level in thirty-eight healthy participants to measure arterial, venous, and CSF flow rates. Each participant underwent two RT-PC sessions: one with eyes open and another with eyes closed, following a 30-minute in-scanner eyes-closed rest period. Frequency-domain analysis quantified power within LFO, respiratory, and cardiac bands across artery, vein, net arteriovenous flow (A + V), and CSF signals. Time domain analysis was used to calculate arterial-to-venous delays (A-V delay) for each pulsation type. Cardiac pulsations dominated the flow rate oscillations, accounting for 95.2%, 85.1%, 81.2%, and 94.2% of the total power in artery, vein, A + V, and CSF, respectively. LFO contributions were lower, accounting for 3.2%, 4.9%, 3.5%, and 0.8%. After 30 min of rest, LFO power increased significantly and consistently in all compartments (p < 0.01) but remained a minor component of the overall oscillatory signal. Time domain analysis revealed a longer A–V delay in the LFO band (318 ms) compared to the cardiac band (82 ms), with both delays showing no change after rest (p > 0.1). Quantitative flow analysis demonstrated that LFOs contributed substantially less to blood and CSF flow oscillations than cardiac pulsations at the cervical level. However, LFO power increased significantly and consistently after rest in blood and CSF, supporting its role as a driver of fluid circulation during drowsiness. Notably, the detection of increased LFO power in arterial blood at the cervical level—upstream of cerebral flow—suggests a potential link to autonomic regulation of vascular tone.