Age- and time-of-day dependence of glymphatic function in the human brain measured via two diffusion MRI methods

Guangxu Han; Ying Zhou; Kemeng Zhang; Bingjie Jiao; Junwen Hu; Yifan Zhang; Zejun Wang; Min Lou; Ruiliang Bai

doi:10.3389/fnagi.2023.1173221

Age- and time-of-day dependence of glymphatic function in the human brain measured via two diffusion MRI methods

Front Aging Neurosci. 2023 May 22:15:1173221. doi: 10.3389/fnagi.2023.1173221. eCollection 2023.

Authors

Guangxu Han^#^{1

2}, Ying Zhou^#³, Kemeng Zhang³, Bingjie Jiao^{1

2}, Junwen Hu^{4

5}, Yifan Zhang^{1

2}, Zejun Wang^{1

2}, Min Lou³, Ruiliang Bai^{1

2

6}

Affiliations

¹ Department of Physical Medicine and Rehabilitation of the Affiliated Sir Run Shaw Hospital AND Interdisciplinary Institute of Neuroscience and Technology, School of Medicine, Zhejiang University, Hangzhou, China.
² Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China.
³ Department of Neurology, School of Medicine, The Second Affiliated Hospital of Zhejiang University, Hangzhou, China.
⁴ Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
⁵ Clinical Research Center for Neurological Diseases of Zhejiang Province, Hangzhou, China.
⁶ MOE Frontier Science Center for Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.

^# Contributed equally.

Abstract

Advanced age, accompanied by impaired glymphatic function, is a key risk factor for many neurodegenerative diseases. To study age-related differences in the human glymphatic system, we measured the influx and efflux activities of the glymphatic system via two non-invasive diffusion magnetic resonance imaging (MRI) methods, ultra-long echo time and low-b diffusion tensor imaging (DTI_low-b) measuring the subarachnoid space (SAS) flow along the middle cerebral artery and DTI analysis along the perivascular space (DTI-ALPS) along medullary veins in 22 healthy volunteers (aged 21-75 years). We first evaluated the circadian rhythm dependence of the glymphatic activity by repeating the MRI measurements at five time points from 8:00 to 23:00 and found no time-of-day dependence in the awake state under the current sensitivity of MRI measurements. Further test-retest analysis demonstrated high repeatability of both diffusion MRI measurements, suggesting their reliability. Additionally, the influx rate of the glymphatic system was significantly higher in participants aged >45 years than in participants aged 21-38, while the efflux rate was significantly lower in those aged >45 years. The mismatched influx and efflux activities in the glymphatic system might be due to age-related changes in arterial pulsation and aquaporin-4 polarization.

Keywords: aging; diffusion MRI; efflux; glymphatic system; influx; time-of-day.

Grants and funding

This study was supported by the STI2030-Major Projects of China (grant 2022ZD0206000 to RB), the National Natural Science Foundation of China (NSFC) (grant 82222032 to RB), and the Natural Science Foundation of Zhejiang Province, China (grant LR20H180001 to RB).