Figure 1.

a, Overview of tracer transport in subarachnoid CSF and PVSs. b, In the healthy brain, arterial pulse waves propagate the perivascular CSF via the subarachnoid space (SAS), driving a convective CSF influx into the brain, where it exchanges with the ISF to drive the glymphatic system, here shown in a simplified model. c, We hypothesized that hypertension-induced vascular pathology, including stiffening and reduced elasticity of the vessel wall, diminishes the ability of the arterial pulse waves to propagate the perivascular CSF, thus reducing influx of CSF into the brain in hypertensive rats. d, Here, the complex intracranial space of CSF, PVSs, brain parenchyma, Virchow–Robin spaces, ISF, and vasculature was segmented into two simplified compartments: CSF and brain based on MR images. In these two compartments, TCCs were measured as the average Gd-DOTA concentration over time. e, A one-tissue compartment was fitted to the TCCs of the two compartments using the CSF TCC as the input function and the brain TCC as the tissue function. From this, we calculated the glymphatic influx rate K₁ and efflux rate constant k₂. f, In the case of whole-brain analysis, partial volume effects and imperfect segmentation of the intracranial space can lead to inclusion of CSF in the brain compartment. This inclusion is modeled as the volume of CSF (V_CSF), analogous to the blood volume in classical kinetic analysis.