Comparative Analysis by Magnetic Resonance Imaging of Extracellular Space Diffusion and Interstitial Fluid Flow in the Rat Striatum and Thalamus

Abstract

Drug delivery to the brain remains a challenge due to the blood–brain barrier. Localized injection of drug therapies represents a promising alternative once the diffusion characteristics of different brain regions have been evaluated. Extracellular space diffusion and interstitial fluid flow of the striatum and thalamus in the rat brain were simultaneously compared using magnetic resonance imaging and the tracer gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA). The diffusion parameters, volume distribution, and half-life time were quantified. While there was extensive diffusion of Gd-DTPA in the striatum, Gd-DTPA was rapidly cleared and had a shorter half-life time in the thalamus. The increased clearance rate and shorter half-life of the tracer in the thalamus were associated with increased expression of Aquaporin-4. The tortuosity of the extracellular space did not show a statistically significant difference between the two regions examined. Our research provides a new reference for brain interstitial drug delivery to treat central nervous system diseases and a better understanding of the brain microenvironment.