Enhanced Dynamic Glymphatic Activity Using Low-intensity Ultrasound in Alzheimer’s Disease

Abstract

Objective To investigate the efficacy and safety of low-intensity ultrasound (LIUS) using serial intravenous contrast-enhanced T1 mapping for the quantitative evaluation of glymphatic activity change and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) for the evaluation of blood-brain barrier(BBB) integrity in various brain regions in patient with Alzheimer’s dementia (AD).

Methods In this prospective study, 10 patients with prodromal AD and early AD (mean age, 69 years ± 9.2 [standard deviation]; 8 women) underwent LIUS sessions for 4 weeks in the outpatient department and two cycles of MRI (pre-LIUS and post-LIUS cycles). For each cycle, T1 maps were acquired at baseline and 30 minutes, 43.5 minutes, and 10 hours after intravenous contrast material injection in regular daytime. The time (min-T) to reach the minimum T1 value (T1min), the absolute difference between baseline T1 and T1min (peak delta T1), and the slope between two measurements at 30 minutes and 10 hours (slope[30minutes-10h]) were determined from T1 value-time curves in cerebral gray matter (GM), cerebral white matter (WM), cerebellar GM, cerebellar WM, and putamen.

Results The slope(30minutes-10h) increased from the pre-LIUS to post-LIUS series in only cerebral GM (mean ratio [post-LIUS/preLIUS] = 1.3395 [2.0125/1.5179], ; P = 0.034). The slope (30minutes-10h) of other brain regions (cerebellar GM, cerebral WM, cerebellar WM, putamen) were not significantly different in between sonication. The Ktrans and Vp of DCE MRI in all brain regions (including frontal, temporal cortex, choroid plexus, and hippocampus) showed no significant difference in between LIUS treatments. There was no newly appeared focal abnormal lesion in brain parenchyma including edema, and microbleeds on T2WI and SWI, respectively after LIUS sessions.

Conclusion In this study, we conjectured that LIUS significantly enhances the glymphatic activity function in the patient with AD.