The discovery of the glymphatic system and its role in clearance of metabolic by-products and toxic protein derivatives has important implications in the development of neurodegenerative disease. 

Develop a non-invasive MRI method to measure glymphatic clearance.

To identify dysfunction of this system requires quantification of clearance rates in both normal and in disease states.  Our pilot study investigated the feasibility of using arterial spin labeling with “single shot” 3D echo planar imaging which allows for whole brain signal acquisition in 100 milliseconds.   Signal strength average was determined in standardized region of interest volumes corrected for pulse per second in 3 bilateral brain regions: temporal, parietal, and frontal lobes before and after exercise.   Seven acquisition times corrected for pulse/sec were plotted using best fit linear regression.  The slope represented rate of clearance (signal strength/pulse).   We studied 18 normals ages 18-70, and 3 subjects with mild clinically diagnosed Alzheimer disease.

We found differences in clearances among all six brain regions in all three age ranges. Pre and post exercise results also differed. The three AD subject pre-exercise clearances were flatter, distinctly outside the range of normal subjects in all brain regions.  Post-exercise in AD group was uninterpretable due to unachievable target heart rate. Descriptive statistics (means, standard deviations, effect sizes) were computed at each level of exercise (pre, post, and change (post-pre), for each section, each age group, and for each brain region in both non-dominant and dominant hemispheres.  Cohen’s d effect size was computed for paired differences between pre and post measures (d=0.20, small; d=0.50, medium; d=0.80, large). 

This pilot study demonstrates the feasibility of using arterial spin labeling with “single shot” 3D Echo planar imaging to quantitate glymphatic clearance and differentiate normal from neurodegenerative disease.  Refinement of this technique in a larger trial is warranted.