Figure 1. Paravascular influx of paramagnetic contrast.

(A) 3D visualization of key anatomical structures in the rat brain prior to administration of contrast. The anatomical structures include the pituitary (light blue), hippocampus (green), superior colliculus (orange), inferior colliculus (dark blue), pineal gland (yellow), and relevant arterial segments (red). The olfactory artery (OA), azygos of the anterior cerebral artery (azACA), azygos pericallosal artery (AzPA), the middle internal frontal artery (IFA), and the posterior lateral choroidal arterial complex were visualized. (B) A 2-dimensional T1-weighted MRI with the color-coded anatomical structures displayed. (C–E) The time series demonstrates early influx of the small molecular weight paramagnetic contrast agent Gd-DTPA (MW 938 Da). (C) The time at which the intrathecally infused Gd-DTPA appears in the cisterna magna is defined as 0 minutes, and (D and E) the earliest part of the influx process is demonstrated in the subsequent time frames and shows that Gd-DTPA enters the brain along paravascular pathways. (F–H) The dynamic time series of early influx of the large molecular weight paramagnetic contrast agent GadoSpin (MW 200 kDa) also shows that transport into the brain is paravascular. Note that it is evident that even though the 2 paramagnetic contrast agents differ in molecular weight, they pass through paravascular conduits at similar rates, supporting that CSF bulk flow governs this process. (I and J) Paravascular transport of the paramagnetic contrast agent is demonstrated particularly clearly at the level of the Circle of Willis along the internal carotid (IC) artery, posterior communicating (Pcom) arteries, and lateral orbitofrontal artery. Scale bar: 3 mm.