Single-shot simultaneous BOLD and velocity-encoding MRI for functional and slow-flow imaging

Cerebrospinal fluid (CSF) motion is coupled with global blood oxygenation level-dependent (BOLD) fluctuations, but the spatial relationship between regional brain activity and CSF dynamics remains poorly understood. Here, we developed a single-shot BOLD-VENC sequence that combines gradient-echo BOLD imaging with spin-echo velocity encoding following the same RF excitation, enabling simultaneous measurement of brain-wide BOLD activity and spatially resolved slow CSF velocity at 3T. The velocity measurement was validated in a slow-flow phantom and in five healthy participants using paced-breathing, breath-holding, and visual-stimulation experiments. Phantom measurements showed strong agreement with prescribed velocities over 0.1-1.0 mm/s (R2 = 0.93-0.98). In vivo measurements demonstrated respiratory- and cardiac-dependent changes in CSF velocity magnitude and direction across the ventricles and cortical subarachnoid spaces (SAS). The established coupling between the negative derivative of the global BOLD signal and fourth-ventricle CSF inflow was reproduced, with a peak lag of 0.9 s. Global BOLD fluctuations were also coupled with spatially distributed CSF velocity changes across ventricular and cortical CSF spaces, with a similar peak lag of 1.2 s. During visual checkerboard stimulation, BOLD-CSF velocity coupling was localized primarily to the SAS surrounding the activated visual cortex, demonstrating a regional relationship between local BOLD activity and nearby CSF motion. These findings establish the feasibility of simultaneous BOLD and slow CSF velocity imaging and extend BOLD-CSF coupling from a global measure toward spatially resolved assessment of hemodynamic-CSF interactions.