Abstract
The recently proposed glymphatic pathway for solute transport and waste clearance from the brain has been the focus of intense debate. By exploiting an isotopically enriched MRI tracer, H217O, we directly imaged glymphatic water transport in the rat brain in vivo. Our results reveal glymphatic transport that is dramatically faster and more extensive than previously thought and unlikely to be explained by diffusion alone. Moreover, we confirm the critical role of aquaporin-4 channels in glymphatic transport.
Authors
Mohammed S. Alshuhri, Lindsay Gallagher, Lorraine M. Work, William M. Holmes
Figure 1
Serial MRI using H217O tracer reveals rapid glymphatic flow over whole brain.
Options:
View larger image
(or click on image)
Download as PowerPoint
(A ) Study design. Rats received infusion of tracer via cisterna magna. Baseline MRI was acquired, followed by infusion of tracer and continuous MRI. (B ) Representative sagittal MRI demonstrating the temporal evolution of tracer over 85 minutes of recording. Normalized pseudocolor scaling illustrates tracer distribution of the 90% 17O-enriched water (MW, 19 Da) (upper panel) and the paramagnetic tracer Gd-DTPA (Magnevist; MW, 938 Da) (bottom panel), where white in the color bar indicates maximum signal change. Representative arrival time maps. The upper panel images show a rat infused with H217O, and the bottom panel images show 1 rat infused with Gd-DTPA. (C ) Corresponding tracer arrival time maps for 4 sagittal slices. White color indicates that the tracer did not arrive within the 85-minute recording. (D ) Summary data showing the normalized percentage signal change as a function of time for H217O (n = 6, blue circles) and Gd-DTPA (n = 6, red circles) for the cerebellum, cisterna magna and frontal cortex. Blue shading on schematic drawing illustrates the location of ROIs. Blue shading on graphs indicates period of tracer infusion. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Data are presented as mean ± SD.
