Figure 2

Glymphatic transport of Gd-DOTA in whole mouse brain by T1 mapping. (A) Proton-density weighted (PDW) MRIs of the brain from a control mouse displayed in three orthogonal planes to highlight landmarks of interest. Cb = Cerebellum; Th = Thalamus; Olf = Olfactory Bulb; 3rd V = 3rd cerebral ventricle; Bs = brainstem; Hp = hippocampus; CC = corpus callosum. Scale bar = 2 mm. (B) Corresponding color-coded T1 map of control mouse brain illustrating that CSF areas are characterized by high T1 values (> 3000 ms) and brain tissue by T1 values of ~ 2000 ms. (C) A color coded T1 map from mouse brain 1 h after Gd-DOTA into CSF. Glymphatic transport of Gd-DOTA is evidenced by the lower T1 values (blue color) in several brain regions when compared to the control mouse in B. (D) Statistical analysis using Welch’s t-test (unequal variance t-test), (Bonferroni correction not applied) of brain regional T1 values with the two conditions (CSF Gd-DOTA versus CSF saline) across groups revealed significant differences in all preselected regions (brainstem ***p < 0.0001; cerebellum ***p < 0.0001; hippocampus **p < 0.001; hypothalamus ***p < 0.0001; midbrain ***p < 0.0001; Olfactory bulb ***p < 0.0001; thalamus **p < 0.002). Data are presented as mean ± SEM. (E) Voxels in the brain with a T1 of 1–1800 ms are captured and converted into a 3D volume rendered binary map (green) in a mouse receiving CSF saline. (F) 3D volume rendered GS-clusters with a similar T1 threshold of 1–1800 ms converted into a binary map (green) from a KX anesthetized mouse 1 h after Gd-DOTA. In the Gd-DOTA mouse the GS-cluster of Gd-DOTA incorporates large parts of the whole brain and is also seen along the middle cerebral artery (MCA) when compared to the control mouse. Scale bar = 1 mm. Figure 2B,C were created using PMOD software Version 3.908, PMOD Technologies LLC. Figure 2E,F were created using Amira version 6.5.0, Thermo Fischer Scientific.