Figure 2 The CSF tracer enriches the extravascular compartment of the brain centripetally. The images present tracer enrichment within brain tissue, while tracer in CSF spaces has been subtracted. The degree of tracer enrichment in brain tissue is expressed by the MRI signal increase, and shown by the colour scale. Tracer enrichment was brain-wide and comparable between the groups at the last MRI scan on Day 1 preceding sleep deprivation. The average percentage signal increase in the brain after 4.57 h is shown for all subjects within (A) the sleep deprivation (n = 7) and (B) sleep (n = 17) groups. For both groups, it should be noted that tracer enrichment occurred in a centripetal pattern, and concentrated particularly in brain regions adjacent to large artery trunks at the surface. The coronal section (middle) shows enhancement in the medial temporal lobe close to the circle of Willis and posterior cerebral arteries, in the cingulum adjacent to the location of the anterior cerebr

Compared to before tracer administration (blue), the normalized T1 signal had increased markedly after 4.57 h (red) within grey matter of cerebral cortex (C) and cerebral white matter (D).

The two groups were comparable with regard to age, gender and tentative diagnosis. The level of tracer in CSF space was similar throughout the study period and should therefore have not confounded different levels of tracer in brain tissue at any time point. In the end, we therefore regard the sleep intervention to be the only factor accompanied with impaired clearance of tracer from the brain in the sleep deprivation group. Total sleep deprivation was verified in the sleep deprivation group by the patient, the attending family members and nursing staff within the neurosurgical ward, where the participants stayed. It was established many years ago that acute sleep deprivation negatively affects a wide range of cognitive functions, D o w n o a d e d l f r o m h t t p s : / / a c a d e m c . o u p . c o m b r a n a r t i c e 1 4 4 3 8 6 3 6 2 1 4 9 1 7 b y g u e s t i / i / l / / / / o n 1 7 A p r i l 2 0 2 4

Sleep and cerebral molecular clearance BRAIN 2021: 144; 863874 | 869 Figure 3 Brain-wide CSF tracer enrichment over time for one individual from the sleep group. The images present tracer enrichment within brain tissue, while tracer in CSF spaces have been subtracted. Standardized T1-weighted MRI was obtained at different time points before and after intrathecal gadobutrol, serving as CSF tracer. Percentage T1 signal increase from tracer enrichment in brain tissue is illustrated by the colour scale. Positive and negative image noise are coded blue or transparent, respectively. Because of a lower signal-to-noise ratio, noise is most apparent in images from time points with no tracer enrichment in the brain. After 4 weeks, there was no sign of residual tracer in brain tissue (Supplementary Table 4).