Glymphatic influx is negatively correlated with cerebral blood volume in male mice

The glymphatic system clears brain waste via cerebrospinal fluid (CSF) influx along perivascular spaces. While vasomotion (0.1-0.3 Hz vessel diameter oscillations) is a known driver of perivascular transport, it is unclear whether slower, tonic vascular changes-reflected by macroscopic cerebral blood volume (CBV)-also influence glymphatic function. Using multimodal mouse MRI, we quantify glymphatic influx, CBV, and CSF volume across six conditions: isoflurane, awake, isoflurane/dexmedetomidine, dexmedetomidine, caffeine, and ketamine/xylazine. Glymphatic influx increases with isoflurane/dexmedetomidine, dexmedetomidine, caffeine, and ketamine/xylazine but decreases with isoflurane versus awake. Across states, glymphatic influx correlates negatively with CBV and positively with extra-ventricular CSF volume. These findings indicate CBV may serve as a consciousness-independent, tonic vascular component that complements dynamic drivers such as vasomotion, suggesting CBV modulation as a potential strategy to enhance waste clearance in protein-aggregation diseases.