BOLD-CSF dynamics assessed using real-time phase contrast CSF flow interleaved with cortical BOLD MRI

BACKGROUND: Cerebrospinal fluid (CSF) motion and pulsatility has been proposed to play a crucial role in clearing brain waste. Although its driving forces remain debated, increasing evidence suggests that large amplitude vasomotion drives such CSF fluctuations. Recently, a fast blood-oxygen-level-dependent (BOLD) fMRI sequence was used to measure the coupling between CSF fluctuations and low-frequency hemodynamic oscillations in the human cortex. However, this technique is not quantitative, only captures unidirectional flow and is sensitive to B0-fluctuations. Real-time phase contrast (pcCSF) instead measures CSF flow dynamics in a fast, quantitative, bidirectional and B0-insensitive manner, but lacks information on hemodynamic brain oscillations. In this study we propose to combine the strengths of both sequences by interleaving real-time phase contrast with a cortical BOLD scan, thereby enabling the quantification of the interaction between CSF flow and cortical BOLD. METHODS: Two experiments were performed. First, we compared the CSF flow measured using real-time phase contrast (pcCSF) with the inflow-sensitized BOLD (iCSF) measurements by interleaving both techniques at the repetition level and planning them at the same location. Next, we compared the BOLD-CSF coupling obtained using the novel pcCSF interleaved with cortical BOLD to the coupling obtained with the original iCSF. To time-lock the CSF fluctuations, participants were instructed to perform slow, abdominal paced breathing. RESULTS: pcCSF captures bidirectional CSF dynamics with a more pronounced in- and outflow curve than the original iCSF method. With the pcCSF method, the BOLD-CSF coupling was stronger (mean cross-correlation peak increase = 0.22, p = .008) and with a 1.9 s shorter temporal lag (p = .016), as compared to using the original iCSF technique. CONCLUSIONS: In this study, we introduce a new method to study the coupling of CSF flow measured in the fourth ventricle to cortical BOLD fluctuations. In contrast to the original approach, the use of phase contrast MRI to measure CSF flow provides a quantitative in- and outflow curve, and improved BOLD-CSF coupling metrics.