Objective: To determine the feasibility of 3D TGSE PASL MRI with long inversion times to estimate CNS perfusion clearance, comparing normals to Alzheimer disease patients.
Methods: This pilot study used 3D TGSE PASL MRI with long TIs to estimate the signal clearance of labeled blood/ultra-filtrate (CSF) from brain signal averages of seven inversion times (TI) from six regions of the brain in 18 normal subjects of ages 18-70 years before and after exercise. Arterial pulse corrected signal average per TI versus TI was plotted. The slope (linear regression) indicated the clearance rate. Three subjects with mild Alzheimer disease (AD) were studied pre-exercise only.
Results: In normals, signal decay rate variance among brain regions, age groups and post-exercise failed to demonstrate statistical significance except in middle-age group pre- to post-exercise-dominant temporal lobe. We found highly statistically significant reduced signal clearance rate in the AD group.
Discussion: Signal decay in normal age groups correlates with decay of T1blood, thus CSF paravascular flow egresses and is inseparable from venous outflow. The AD group correlates with decay rate T1CSF, indicating a proportion of labeled blood ultra-filtered within the brain (paravascular fluid) is retained. This provides indirect evidence of reduced paravascular clearance in AD. Further development may produce an efficient biomarker identifying neurodegenerative diseases and future treatment efficacy.
Keywords: 3D TGSE (turbo gradient spin echo) PASL (pulsed arterial spin labeling) MRI imaging; Alzheimer Disease; Arterial spin labeling perfusion MRI; Glymphatic system; Paravascular flow.