Glymphatic clearance function in patients with cerebral small vessel disease

Abstract

Few studies have focused on the connection between glymphatic dysfunction and cerebral small vessel disease (CSVD), partially due to the lack of non-invasive methods to measure glymphatic function. We established modified index for diffusion tensor image analysis along the perivascular space (mALPS-index), which was calculated on diffusion tensor image (DTI), compared it with the classical detection of glymphatic clearance function calculated on Glymphatic MRI after intrathecal administration of gadolinium (study 1), and analyzed the relationship between CSVD imaging markers and mALPS-index in CSVD patients from the CIRCLE study (ClinicalTrials.gov ID: NCT03542734) (study 2). Among 39 patients included in study 1, mALPS-index were significantly related to glymphatic clearance function calculated on Glymphatic MRI ( r = -0.772~-0.844, p < 0.001). A total of 330 CSVD patients were included in study 2. Severer periventricular and deep white matter hyperintensities (β = -0.332, p < 0.001; β = -0.293, p < 0.001), number of lacunas (β = -0.215, p < 0.001), number of microbleeds (β = -0.152, p = 0.005), and severer enlarged perivascular spaces in basal ganglia (β = -0.223, p < 0.001) were related to mALPS-index. Our results indicated that non-invasive mALPS-index might represent glymphatic clearance function, which could be applied in clinic in future. Glymphatic clearance function might play a role in the development of CSVD.

Keywords: Cerebral small vessel disease; Enlarged perivascular spaces; Glymphatic pathway; Lacunas; Microbleeds; White matter hyperintensities.