Ventricular CSF-to-blood water transport kinetics in adult hydrocephalus

Water exchange between cerebrospinal fluid (CSF) and blood is fundamental to brain fluid homeostasis, yet ventricular CSF-to-blood water transport has never been quantified as a physiological parameter in adult humans. We investigated ventricular water absorption kinetics in 40 adults undergoing diagnostic evaluation for hydrocephalus. During ventricular infusion testing, ¹⁵O-labelled water was administered intraventricularly via an external ventricular drain, with continuous jugular bulb blood sampling and simultaneous intracranial pressure (ICP) monitoring. Ventricular water absorption was estimated using non-parametric population pharmacokinetic modelling of venous radioactivity-time curves. Model performance demonstrated robust individual parameter estimation. Ventricular water absorption showed substantial inter-individual variability (mean half-time 65.2 ± 34.3 s; range 31.5-196.8 s). Absorption kinetics were not associated with static or pulsatile ICP metrics (overnight or during infusion), ventricular volume or surface area, or CSF-blood osmotic gradients. No associations were observed with demographic variables. A modest positive association was detected with the CSF-blood protein concentration difference. These findings establish ventricular CSF-to-blood water transport as a quantifiable physiological metric in adult hydrocephalus and suggest that ventricular water exchange is regulated independently of global intracranial pressure and ventricular morphology, consistent with intrinsic barrier and microvascular exchange mechanisms.